首页 > 最新文献

Molecular and Cellular Endocrinology最新文献

英文 中文
Melatonin improves nitric oxide bioavailability in isoproterenol induced myocardial injury 褪黑素可提高一氧化氮在异丙肾上腺素诱导的心肌损伤中的生物利用率
IF 4.1 3区 医学 Q1 Biochemistry, Genetics and Molecular Biology Pub Date : 2024-05-24 DOI: 10.1016/j.mce.2024.112279
Ramison Santos , Patrick Turck , Victor de Mello Palma , Fernanda Visioli , Vanessa Duarte Ortiz , Isabel Cristina Teixeira Proença , Tânia Regina G. Fernandes , Elissa Fernandes , Silvio Tasca , Cristina Campos Carraro , Adriane Belló-Klein , Alex Sander da Rosa Araujo , Neelam Khaper , Alexandre Luz de Castro

Isoproterenol administration is associated with cardiac inflammation and decreased NO availability. Melatonin has been reported to have cardioprotective effect. The aim of this study was to investigate the effect of melatonin on NO bioavailability and inflammation in myocardial injury induced by isoproterenol. Isoproterenol was administrated in male Wistar rats for 7 days to induce cardiac injury. The animals were divided into 3 groups: Control, Isoproterenol, Isoproterenol + Melatonin. Animals received melatonin for 7 days. Echocardiographic analysis was performed and the hearts were collected for molecular analysis. Animals that received isoproterenol demonstrated a reduction in left ventricle systolic and diastolic diameter, indicating the presence of concentric hypertrophy. Melatonin was able to attenuate this alteration. Melatonin also improved NO bioavailability and decreased NF-κβ, TNFα and IL-1β expression. In conclusion, melatonin exhibited a cardioprotective effect which was associated with improving NO bioavailability and decreasing the pro-inflammatory proteins.

异丙肾上腺素与心脏炎症和氮氧化物供应减少有关。据报道,褪黑素具有保护心脏的作用。本研究旨在探讨褪黑素对异丙托品醇诱导的心肌损伤中 NO 生物利用率和炎症的影响。给雄性 Wistar 大鼠注射异丙肾上腺素 7 天以诱导心肌损伤。动物被分为 3 组:对照组、异丙肾上腺素组、异丙肾上腺素+褪黑素组。动物接受褪黑素治疗 7 天。进行超声心动图分析,并收集心脏进行分子分析。接受异丙肾上腺素治疗的动物显示左心室收缩和舒张直径缩小,表明存在同心性肥厚。褪黑素能够减轻这种变化。褪黑激素还改善了氮氧化物的生物利用率,降低了 NF-κβ、TNFα 和 IL-1β 的表达。总之,褪黑素具有保护心脏的作用,这与改善氮氧化物生物利用率和减少促炎蛋白有关。
{"title":"Melatonin improves nitric oxide bioavailability in isoproterenol induced myocardial injury","authors":"Ramison Santos ,&nbsp;Patrick Turck ,&nbsp;Victor de Mello Palma ,&nbsp;Fernanda Visioli ,&nbsp;Vanessa Duarte Ortiz ,&nbsp;Isabel Cristina Teixeira Proença ,&nbsp;Tânia Regina G. Fernandes ,&nbsp;Elissa Fernandes ,&nbsp;Silvio Tasca ,&nbsp;Cristina Campos Carraro ,&nbsp;Adriane Belló-Klein ,&nbsp;Alex Sander da Rosa Araujo ,&nbsp;Neelam Khaper ,&nbsp;Alexandre Luz de Castro","doi":"10.1016/j.mce.2024.112279","DOIUrl":"10.1016/j.mce.2024.112279","url":null,"abstract":"<div><p>Isoproterenol administration is associated with cardiac inflammation and decreased NO availability. Melatonin has been reported to have cardioprotective effect. The aim of this study was to investigate the effect of melatonin on NO bioavailability and inflammation in myocardial injury induced by isoproterenol. Isoproterenol was administrated in male Wistar rats for 7 days to induce cardiac injury. The animals were divided into 3 groups: Control, Isoproterenol, Isoproterenol + Melatonin. Animals received melatonin for 7 days. Echocardiographic analysis was performed and the hearts were collected for molecular analysis. Animals that received isoproterenol demonstrated a reduction in left ventricle systolic and diastolic diameter, indicating the presence of concentric hypertrophy. Melatonin was able to attenuate this alteration. Melatonin also improved NO bioavailability and decreased NF-κβ, TNFα and IL-1β expression. In conclusion, melatonin exhibited a cardioprotective effect which was associated with improving NO bioavailability and decreasing the pro-inflammatory proteins.</p></div>","PeriodicalId":18707,"journal":{"name":"Molecular and Cellular Endocrinology","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2024-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141133074","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Mesenchymal stem cells improve cardiac function in diabetic rats by reducing cardiac injury biomarkers and downregulating JAK/STAT/iNOS and iNOS/Apoptosis signaling pathways 间充质干细胞通过减少心脏损伤生物标志物和下调 JAK/STAT/iNOS 和 iNOS/Apoptosis 信号通路,改善糖尿病大鼠的心脏功能
IF 4.1 3区 医学 Q1 Biochemistry, Genetics and Molecular Biology Pub Date : 2024-05-24 DOI: 10.1016/j.mce.2024.112280
Thoraya Mohamed Elhassan A-Elgadir , Ayed A. Shati , Saif Aboud Alqahtani , Hasnaa A. Ebrahim , Hailah M. Almohaimeed , Asmaa M. ShamsEldeeen , Mohamed A. Haidara , Samaa S. Kamar , Amal F. Dawood , Mahmoud H. El-Bidawy

Cardiovascular complications are prevalent manifestations of type 2 diabetes mellitus (T2DM) and are usually the main cause of death. This study aims to show the underlying mechanisms of the potential therapeutic effect of mesenchymal stem cells (MSCs) on diabetic cardiac dysfunction. Twenty-four male Wistar rats were randomly assigned to one of three groups The control group received standard laboratory chow, and the groups with T2DM received a single dose of 45 mg/kg body weight of streptozotocin (STZ) after 3 weeks of pretreatment with a high-fat diet (HFD). Eight weeks after the diagnosis of T2DM, rats were divided into two groups: the T2DM model group and the T2DM + MSCs group. BM-MSCs were administered systemically at 2 × 106 cells/rat doses.

A Significant amelioration in Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) and dyslipidemia was noted 2 weeks post-administration of MSCs. Administration of MSCs improved dyslipidemia, the altered cardiac injury biomarkers (p ≤ 0.0001), downregulated Janus kinase 2/signal transducer and activator of transcription 3(JAK2/STAT3)/inducible Nitric oxide synthase (iNOS) and iNOS/Apoptosis signaling pathways. This was associated with improved cardiac dysfunction (impaired left ventricular performance and decreased contractility index).

Our results show that MSCs ameliorate cardiac dysfunction associated with diabetic cardiomyopathy by lowering dyslipidemia and insulin resistance, inhibiting oxidative stress, and inflammation, downregulating JAK2/STAT3/iNOS and iNOS/Apoptosis signaling pathways.

心血管并发症是2型糖尿病(T2DM)的常见表现,通常是导致死亡的主要原因。本研究旨在揭示间充质干细胞(MSCs)对糖尿病心脏功能障碍的潜在治疗作用的内在机制。24只雄性Wistar大鼠被随机分配到三组中的一组。对照组接受标准实验室饲料,T2DM组在高脂饮食(HFD)预处理3周后接受单剂量45毫克/公斤体重的链脲佐菌素(STZ)。确诊 T2DM 八周后,大鼠被分为两组:T2DM 模型组和 T2DM + 间充质干细胞组。给药两周后,大鼠的胰岛素抵抗静态模型评估(HOMA-IR)和血脂异常明显改善。服用间叶干细胞可改善血脂异常、心脏损伤生物标志物的改变(p ≤ 0.0001)、Janus 激酶 2/信号转导和激活转录 3(JAK2/STAT3)/诱导一氧化氮合酶(iNOS)和 iNOS/细胞凋亡信号通路的下调。我们的研究结果表明,间充质干细胞可通过降低血脂异常和胰岛素抵抗、抑制氧化应激和炎症、下调 JAK2/STAT3/iNOS 和 iNOS/Aoptosis 信号通路,改善糖尿病心肌病相关的心脏功能障碍。
{"title":"Mesenchymal stem cells improve cardiac function in diabetic rats by reducing cardiac injury biomarkers and downregulating JAK/STAT/iNOS and iNOS/Apoptosis signaling pathways","authors":"Thoraya Mohamed Elhassan A-Elgadir ,&nbsp;Ayed A. Shati ,&nbsp;Saif Aboud Alqahtani ,&nbsp;Hasnaa A. Ebrahim ,&nbsp;Hailah M. Almohaimeed ,&nbsp;Asmaa M. ShamsEldeeen ,&nbsp;Mohamed A. Haidara ,&nbsp;Samaa S. Kamar ,&nbsp;Amal F. Dawood ,&nbsp;Mahmoud H. El-Bidawy","doi":"10.1016/j.mce.2024.112280","DOIUrl":"10.1016/j.mce.2024.112280","url":null,"abstract":"<div><p>Cardiovascular complications are prevalent manifestations of type 2 diabetes mellitus (T2DM) and are usually the main cause of death. This study aims to show the underlying mechanisms of the potential therapeutic effect of mesenchymal stem cells (MSCs) on diabetic cardiac dysfunction. Twenty-four male Wistar rats were randomly assigned to one of three groups The control group received standard laboratory chow, and the groups with T2DM received a single dose of 45 mg/kg body weight of streptozotocin (STZ) after 3 weeks of pretreatment with a high-fat diet (HFD). Eight weeks after the diagnosis of T2DM, rats were divided into two groups: the T2DM model group and the T2DM + MSCs group. BM-MSCs were administered systemically at 2 × 10<sup>6</sup> cells/rat doses.</p><p>A Significant amelioration in Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) and dyslipidemia was noted 2 weeks post-administration of MSCs. Administration of MSCs improved dyslipidemia, the altered cardiac injury biomarkers (p ≤ 0.0001), downregulated Janus kinase 2/signal transducer and activator of transcription 3(JAK2/STAT3)/inducible Nitric oxide synthase (iNOS) and iNOS/Apoptosis signaling pathways. This was associated with improved cardiac dysfunction (impaired left ventricular performance and decreased contractility index).</p><p>Our results show that MSCs ameliorate cardiac dysfunction associated with diabetic cardiomyopathy by lowering dyslipidemia and insulin resistance, inhibiting oxidative stress, and inflammation, downregulating JAK2/STAT3/iNOS and iNOS/Apoptosis signaling pathways.</p></div>","PeriodicalId":18707,"journal":{"name":"Molecular and Cellular Endocrinology","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2024-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141131510","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
L(1)10Bb serves as a conservative determinant for soma-germline communications via cellular non-autonomous effects within the testicular stem cell niche L(1)10Bb通过睾丸干细胞龛内的细胞非自主效应,成为体细胞与胚系沟通的保守决定因素
IF 4.1 3区 医学 Q1 Biochemistry, Genetics and Molecular Biology Pub Date : 2024-05-23 DOI: 10.1016/j.mce.2024.112278
Lei He , Feiteng Sun , Yunhao Wu , Zhiran Li , Yangbo Fu, Qiuru Huang, Jiaxin Li, Zihan Wang, Jiaying Cai, Chenrui Feng, Xiaonan Deng, Han Gu, Xuxin He, Jun Yu, Fei Sun

The testicular stem cell niche is the central regulator of spermatogenesis in Drosophila melanogaster. However, the underlying regulatory mechanisms are unclear. This study demonstrated the crucial role of lethal (1) 10Bb [l(1)10Bb] in regulating the testicular stem cell niche. Dysfunction of l(1)10Bb in early-stage cyst cells led to male fertility disorders and compromised cyst stem cell maintenance. Moreover, the dysfunction of l(1)10Bb in early-stage cyst cells exerted non-autonomous effects on germline stem cell differentiation, independently of hub signals. Notably, our study highlights the rescue of testicular defects through ectopic expression of L(1)10Bb and the human homologous protein BUD31 homolog (BUD31). In addition, l(1)10Bb dysfunction in early-stage cyst cells downregulated the expression of spliceosome subunits in the Sm and the precursor RNA processing complexes. Collectively, our findings established l(1)10Bb as a pivotal factor in the modulation of Drosophila soma-germline communications within the testicular stem cell niche.

睾丸干细胞龛是黑腹果蝇精子发生的核心调节因子。然而,其潜在的调控机制尚不清楚。本研究证明了致死(1)10Bb [l(1)10Bb] 在调节睾丸干细胞龛中的关键作用。早期囊肿细胞中的l(1)10Bb功能失调会导致男性生育障碍,并影响囊肿干细胞的维持。此外,早期囊肿细胞中l(1)10Bb的功能障碍对生殖系干细胞分化产生非自主性影响,与中枢信号无关。值得注意的是,我们的研究强调了通过异位表达L(1)10Bb和人类同源蛋白BUD31同源物(BUD31)来挽救睾丸缺陷。此外,l(1)10Bb在早期囊肿细胞中的功能障碍下调了Sm和前体RNA加工复合物中剪接体亚基的表达。总之,我们的研究结果确定了l(1)10Bb是果蝇睾丸干细胞龛内调节体细胞与胚系沟通的关键因素。
{"title":"L(1)10Bb serves as a conservative determinant for soma-germline communications via cellular non-autonomous effects within the testicular stem cell niche","authors":"Lei He ,&nbsp;Feiteng Sun ,&nbsp;Yunhao Wu ,&nbsp;Zhiran Li ,&nbsp;Yangbo Fu,&nbsp;Qiuru Huang,&nbsp;Jiaxin Li,&nbsp;Zihan Wang,&nbsp;Jiaying Cai,&nbsp;Chenrui Feng,&nbsp;Xiaonan Deng,&nbsp;Han Gu,&nbsp;Xuxin He,&nbsp;Jun Yu,&nbsp;Fei Sun","doi":"10.1016/j.mce.2024.112278","DOIUrl":"https://doi.org/10.1016/j.mce.2024.112278","url":null,"abstract":"<div><p>The testicular stem cell niche is the central regulator of spermatogenesis in <em>Drosophila melanogaster</em>. However, the underlying regulatory mechanisms are unclear. This study demonstrated the crucial role of <em>lethal (1)</em> 10Bb [<em>l(1)</em>10Bb] in regulating the testicular stem cell niche. Dysfunction of <em>l(1)</em>10Bb in early-stage cyst cells led to male fertility disorders and compromised cyst stem cell maintenance. Moreover, the dysfunction of <em>l(1)</em>10Bb in early-stage cyst cells exerted non-autonomous effects on germline stem cell differentiation, independently of hub signals. Notably, our study highlights the rescue of testicular defects through ectopic expression of L(1)10Bb and the human homologous protein BUD31 homolog (BUD31). In addition, <em>l(1)</em>10Bb dysfunction in early-stage cyst cells downregulated the expression of spliceosome subunits in the Sm and the precursor RNA processing complexes. Collectively, our findings established <em>l(1)</em>10Bb as a pivotal factor in the modulation of <em>Drosophila</em> soma-germline communications within the testicular stem cell niche.</p></div>","PeriodicalId":18707,"journal":{"name":"Molecular and Cellular Endocrinology","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2024-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141097483","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
TJP1 suppresses trophoblast cell invasion by expressing E2F8 in the human placenta TJP1 通过在人类胎盘中表达 E2F8 抑制滋养层细胞入侵
IF 4.1 3区 医学 Q1 Biochemistry, Genetics and Molecular Biology Pub Date : 2024-05-23 DOI: 10.1016/j.mce.2024.112277
Rika Miki , Seiko Matsuo , Takafumi Ushida , Sho Tano , Kenji Imai , Akihiro Nawa , Hiroaki Kajiyama , Tomomi Kotani

Adequate extravillous trophoblast (EVT) invasion into the maternal decidua is important for human placental development. We identified that E2F transcription factor 8 (E2F8) suppresses EVT invasion, and that tight junction protein-1 (TJP1) is a potential downstream target gene of E2F8. We investigated the role of TJP1 in the human placenta and regulation of TJP1 expression by E2F8. TJP1 expression decreased in E2F8 knockdown HTR-8/SVneo cells. TJP1 and E2F8 were co-expressed in villi in the first-trimester placenta and in EVTs and villi in the third-trimester placenta. TJP1 was significantly increased in the pre-eclamptic compared with control placenta. TJP1 knockdown increased the invasion of HTR-8/SVneo cells, while TJP1 overexpression inhibited cell invasion. Halo-E2F8 overexpression significantly increased TJP1 expression and TJP1 transcription compared with control placenta. Our findings suggest that E2F8 promotes TJP1 transcription, and that TJP1 expression by E2F8 inhibits EVT invasion. TJP1 and E2F8 may be related to pre-eclampsia pathogenesis.

绒毛外滋养层细胞(EVT)充分侵入母体蜕膜对人类胎盘的发育非常重要。我们发现E2F转录因子8(E2F8)抑制EVT的侵入,而紧密连接蛋白-1(TJP1)是E2F8的潜在下游靶基因。我们研究了 TJP1 在人类胎盘中的作用以及 E2F8 对 TJP1 表达的调控。在 E2F8 敲除的 HTR-8/SVneo 细胞中,TJP1 的表达量减少。TJP1和E2F8在第一妊娠期胎盘的绒毛和第三妊娠期胎盘的EVT和绒毛中共同表达。与对照胎盘相比,子痫前期胎盘中的 TJP1 明显增加。敲除 TJP1 会增加 HTR-8/SVneo 细胞的侵袭,而过表达 TJP1 则会抑制细胞的侵袭。与对照胎盘相比,Halo-E2F8 过表达可显著增加 TJP1 的表达和 TJP1 的转录。我们的研究结果表明,E2F8能促进TJP1的转录,E2F8表达的TJP1能抑制EVT的侵袭。TJP1和E2F8可能与先兆子痫的发病机制有关。
{"title":"TJP1 suppresses trophoblast cell invasion by expressing E2F8 in the human placenta","authors":"Rika Miki ,&nbsp;Seiko Matsuo ,&nbsp;Takafumi Ushida ,&nbsp;Sho Tano ,&nbsp;Kenji Imai ,&nbsp;Akihiro Nawa ,&nbsp;Hiroaki Kajiyama ,&nbsp;Tomomi Kotani","doi":"10.1016/j.mce.2024.112277","DOIUrl":"https://doi.org/10.1016/j.mce.2024.112277","url":null,"abstract":"<div><p>Adequate extravillous trophoblast (EVT) invasion into the maternal decidua is important for human placental development. We identified that E2F transcription factor 8 (E2F8) suppresses EVT invasion, and that tight junction protein-1 (<em>TJP1</em>) is a potential downstream target gene of E2F8. We investigated the role of TJP1 in the human placenta and regulation of TJP1 expression by E2F8. <em>TJP1</em> expression decreased in <em>E2F8</em> knockdown HTR-8/SVneo cells. TJP1 and E2F8 were co-expressed in villi in the first-trimester placenta and in EVTs and villi in the third-trimester placenta. TJP1 was significantly increased in the pre-eclamptic compared with control placenta. <em>TJP1</em> knockdown increased the invasion of HTR-8/SVneo cells, while TJP1 overexpression inhibited cell invasion. Halo-E2F8 overexpression significantly increased <em>TJP1</em> expression and <em>TJP1</em> transcription compared with control placenta. Our findings suggest that E2F8 promotes <em>TJP1</em> transcription, and that TJP1 expression by E2F8 inhibits EVT invasion. TJP1 and E2F8 may be related to pre-eclampsia pathogenesis.</p></div>","PeriodicalId":18707,"journal":{"name":"Molecular and Cellular Endocrinology","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2024-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141097352","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The Guillemin-Yen partnership: A bright light gone dark Guillemin-Yen 合作伙伴关系:黑暗中的曙光
IF 4.1 3区 医学 Q1 Biochemistry, Genetics and Molecular Biology Pub Date : 2024-05-22 DOI: 10.1016/j.mce.2024.112276
Eli Y. Adashi MD, MS
{"title":"The Guillemin-Yen partnership: A bright light gone dark","authors":"Eli Y. Adashi MD, MS","doi":"10.1016/j.mce.2024.112276","DOIUrl":"10.1016/j.mce.2024.112276","url":null,"abstract":"","PeriodicalId":18707,"journal":{"name":"Molecular and Cellular Endocrinology","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2024-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141086675","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
AMPK inhibits voltage-gated calcium channel-current in rat chromaffin cells AMPK 可抑制大鼠绒毛膜细胞中的电压门控钙通道电流。
IF 4.1 3区 医学 Q1 Biochemistry, Genetics and Molecular Biology Pub Date : 2024-05-20 DOI: 10.1016/j.mce.2024.112275
A.K. Fukumoto-Inukai , K. Bermeo , I. Arenas , M.J. Rosendo-Pineda , J.A. Pimentel-Cabrera , D.E. Garcia

Metabolic changes are critical in the regulation of Ca2+ influx in central and peripheral neuroendocrine cells. To study the regulation of L-type Ca2+ channels by AMPK we used biochemical reagents and ATP/glucose-concentration manipulations in rat chromaffin cells. AICAR and Compound-C, at low concentration, significantly induce changes in L-type Ca2+ channel-current amplitude and voltage dependence. Remarkably, an overlasting decrease in the channel-current density can be induced by lowering the intracellular level of ATP. Accordingly, Ca2+ channel-current density gradually diminishes by decreasing the extracellular glucose concentration. By using immunofluorescence, a decrease in the expression of CaV1.2 is observed while decreasing extracellular glucose, suggesting that AMPK reduces the number of functional Ca2+ channels into the plasma membrane. Together, these results support for the first time the dependence of metabolic changes in the maintenance of Ca2+ channel-current by AMPK. They reveal a key step in Ca2+ influx in secretory cells.

代谢变化对中枢和外周神经内分泌细胞的 Ca2+ 流入调节至关重要。为了研究 AMPK 对 L 型 Ca2+ 通道的调控,我们在大鼠绒毛膜细胞中使用了生化试剂和 ATP/葡萄糖浓度操作。低浓度的 AICAR 和化合物-C 能显著诱导 L 型 Ca2+ 通道电流振幅和电压依赖性的变化。值得注意的是,降低细胞内的 ATP 水平可诱导通道电流密度的重叠下降。相应地,随着细胞外葡萄糖浓度的降低,Ca2+ 通道电流密度也会逐渐降低。通过免疫荧光法,在降低细胞外葡萄糖浓度的同时,观察到 CaV1.2 的表达减少,这表明 AMPK 减少了进入质膜的功能性 Ca2+ 通道的数量。这些结果首次证明了 AMPK 在维持 Ca2+ 通道电流时对代谢变化的依赖性。它们揭示了分泌细胞中 Ca2+ 流入的一个关键步骤。
{"title":"AMPK inhibits voltage-gated calcium channel-current in rat chromaffin cells","authors":"A.K. Fukumoto-Inukai ,&nbsp;K. Bermeo ,&nbsp;I. Arenas ,&nbsp;M.J. Rosendo-Pineda ,&nbsp;J.A. Pimentel-Cabrera ,&nbsp;D.E. Garcia","doi":"10.1016/j.mce.2024.112275","DOIUrl":"10.1016/j.mce.2024.112275","url":null,"abstract":"<div><p>Metabolic changes are critical in the regulation of Ca<sup>2+</sup> influx in central and peripheral neuroendocrine cells. To study the regulation of L-type Ca<sup>2+</sup> channels by AMPK we used biochemical reagents and ATP/glucose-concentration manipulations in rat chromaffin cells. AICAR and Compound-C, at low concentration, significantly induce changes in L-type Ca<sup>2+</sup> channel-current amplitude and voltage dependence. Remarkably, an overlasting decrease in the channel-current density can be induced by lowering the intracellular level of ATP. Accordingly, Ca<sup>2+</sup> channel-current density gradually diminishes by decreasing the extracellular glucose concentration. By using immunofluorescence, a decrease in the expression of Ca<sub>V</sub>1.2 is observed while decreasing extracellular glucose, suggesting that AMPK reduces the number of functional Ca<sup>2+</sup> channels into the plasma membrane. Together, these results support for the first time the dependence of metabolic changes in the maintenance of Ca<sup>2+</sup> channel-current by AMPK. They reveal a key step in Ca<sup>2+</sup> influx in secretory cells.</p></div>","PeriodicalId":18707,"journal":{"name":"Molecular and Cellular Endocrinology","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2024-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141081979","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Interleukin-1 increases SERPINE1 expression in human granulosa-lutein cell via P50/P52 signaling pathways 白细胞介素-1 通过 P50/P52 信号通路增加人 Granulosa-Lutein 细胞中 SERPINE1 的表达。
IF 4.1 3区 医学 Q1 Biochemistry, Genetics and Molecular Biology Pub Date : 2024-05-20 DOI: 10.1016/j.mce.2024.112274
Yu Xiang , Shuangying Liu , Shan Wan , Qingqing Chen , Yang Song , Guofang Feng , Xinyue Zhang , Long Bai , Yimin Zhu

It has been reported that immune factors are associated with the occurrence of polycystic ovary syndrome (PCOS). Interleukin-1 (IL-1) is a member of the interleukin family that widely participates in the regulation of the inflammatory response in the immune system. In addition, it has been reported that aberrant IL-1 accumulation in serum is associated with the occurrence of PCOS. However, little is known about how IL-1 participates in the pathogenesis of PCOS. In the present study, we demonstrated that the immune microenvironment was altered in follicular fluid from PCOS patients and that the expression levels of two IL-1 cytokines, IL-1α and IL-1β were increased. Transcriptome analysis revealed that IL-1α and IL-1β treatment induced primary human granulosa-lutein (hGL) cell inflammatory response and increased the expression of serpin family E member 1 (SERPINE1). Mechanistically, we demonstrated that IL-1α and IL-1β upregulated SERPINE1 expression through IL-1R1-mediated activation of downstream P50 and P52 signaling pathways in human granulosa cells. Our study highlighted the role of immune state changes in the occurrence of PCOS and provided new insight into the treatment of patients with IL-1-induced ovarian function disorders.

据报道,免疫因素与多囊卵巢综合征(PCOS)的发生有关。白细胞介素-1(IL-1)是白细胞介素家族的一员,广泛参与调节免疫系统的炎症反应。此外,据报道,血清中 IL-1 的异常积累与多囊卵巢综合症的发生有关。然而,人们对 IL-1 如何参与 PCOS 的发病机制知之甚少。本研究表明,PCOS 患者卵泡液中的免疫微环境发生了改变,两种 IL-1 细胞因子(IL-1α 和 IL-1β)的表达水平升高。转录组分析表明,IL-1α和IL-1β可诱导原代人颗粒-黄体(hGL)细胞炎症反应,并增加丝氨酸蛋白家族E成员1(SERPINE1)的表达。从机理上讲,我们证明了IL-1α和IL-1β通过IL-1R1介导的下游P50和P52信号通路激活人颗粒细胞中SERPINE1的表达。我们的研究强调了免疫状态变化在多囊卵巢综合征发生中的作用,并为治疗IL-1诱导的卵巢功能紊乱患者提供了新的见解。
{"title":"Interleukin-1 increases SERPINE1 expression in human granulosa-lutein cell via P50/P52 signaling pathways","authors":"Yu Xiang ,&nbsp;Shuangying Liu ,&nbsp;Shan Wan ,&nbsp;Qingqing Chen ,&nbsp;Yang Song ,&nbsp;Guofang Feng ,&nbsp;Xinyue Zhang ,&nbsp;Long Bai ,&nbsp;Yimin Zhu","doi":"10.1016/j.mce.2024.112274","DOIUrl":"10.1016/j.mce.2024.112274","url":null,"abstract":"<div><p>It has been reported that immune factors are associated with the occurrence of polycystic ovary syndrome (PCOS). Interleukin-1 (IL-1) is a member of the interleukin family that widely participates in the regulation of the inflammatory response in the immune system. In addition, it has been reported that aberrant IL-1 accumulation in serum is associated with the occurrence of PCOS. However, little is known about how IL-1 participates in the pathogenesis of PCOS. In the present study, we demonstrated that the immune microenvironment was altered in follicular fluid from PCOS patients and that the expression levels of two IL-1 cytokines, IL-1α and IL-1β were increased. Transcriptome analysis revealed that IL-1α and IL-1β treatment induced primary human granulosa-lutein (hGL) cell inflammatory response and increased the expression of serpin family E member 1 (SERPINE1). Mechanistically, we demonstrated that IL-1α and IL-1β upregulated SERPINE1 expression through IL-1R1-mediated activation of downstream P50 and P52 signaling pathways in human granulosa cells. Our study highlighted the role of immune state changes in the occurrence of PCOS and provided new insight into the treatment of patients with IL-1-induced ovarian function disorders.</p></div>","PeriodicalId":18707,"journal":{"name":"Molecular and Cellular Endocrinology","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2024-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141081980","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Polypeptide N-Acetylgalactosaminyl transferase 14 is a novel mediator in pancreatic β-cell function and growth 多肽 N-乙酰半乳糖氨酰基转移酶 14 是胰腺 β 细胞功能和生长的新型介质
IF 4.1 3区 医学 Q1 Biochemistry, Genetics and Molecular Biology Pub Date : 2024-05-18 DOI: 10.1016/j.mce.2024.112269
Tingting Shu , Yan Zhang , Tong Sun , Yunxia Zhu

Polypeptide N-Acetylgalactosaminyl transferase 14 (GALNT14) plays important roles in cancer progression and chemotherapy response. Here, we show that GALNT14 is highly expressed in pancreatic β cells and regulates β cell function and growth. We found that the expression level of Ganlt14 was significantly decreased in the primary islets from three rodent type-2 diabetic models. Single-Cell sequencing defined that Galnt14 was mainly expressed in β cells of mouse islets. Galnt14 knockout (G14KO) INS-1 cell line, constructed by using CRISPR/Cas9 technology were growth normal, but showed blunt shape, and increased basal insulin secretion. Combined proteomics and glycoproteomics demonstrated that G14KO altered cell-to-cell junctions, communication, and adhesion. Insulin receptor (IR) and IGF1-1R were indirectly confirmed for GALNT14 substrates, contributed to diminished IGF1-induced p-AKT levels and cell growth in G14KO cells. Overall, this study uncovers that GALNT14 is a novel modulator in regulating β cells biology, providing a missing link of β cells O-glycosylation to diabetes development.

多肽 N-乙酰半乳糖氨酰转移酶 14(GALNT14)在癌症进展和化疗反应中发挥着重要作用。在这里,我们发现 GALNT14 在胰腺 β 细胞中高表达,并调控 β 细胞的功能和生长。我们发现,在三种啮齿类 2 型糖尿病模型的原代胰岛中,Ganlt14 的表达水平明显下降。单细胞测序确定了Galnt14主要在小鼠胰岛β细胞中表达。利用CRISPR/Cas9技术构建的Galnt14基因敲除(G14KO)INS-1细胞系生长正常,但形状变钝,基础胰岛素分泌增加。蛋白质组学和糖蛋白组学联合研究表明,G14KO 改变了细胞间的连接、交流和粘附。胰岛素受体(IR)和 IGF1-1R 被间接证实为 GALNT14 的底物,有助于降低 IGF1 诱导的 p-AKT 水平和 G14KO 细胞的细胞生长。总之,这项研究发现,GALNT14是调节β细胞生物学的新型调节因子,为β细胞O-糖基化与糖尿病的发生提供了一个缺失的环节。
{"title":"Polypeptide N-Acetylgalactosaminyl transferase 14 is a novel mediator in pancreatic β-cell function and growth","authors":"Tingting Shu ,&nbsp;Yan Zhang ,&nbsp;Tong Sun ,&nbsp;Yunxia Zhu","doi":"10.1016/j.mce.2024.112269","DOIUrl":"10.1016/j.mce.2024.112269","url":null,"abstract":"<div><p>Polypeptide N-Acetylgalactosaminyl transferase 14 (GALNT14) plays important roles in cancer progression and chemotherapy response. Here, we show that GALNT14 is highly expressed in pancreatic β cells and regulates β cell function and growth. We found that the expression level of <em>Ganlt14</em> was significantly decreased in the primary islets from three rodent type-2 diabetic models. Single-Cell sequencing defined that <em>Galnt14</em> was mainly expressed in β cells of mouse islets. <em>Galnt14</em> knockout (G14KO) INS-1 cell line, constructed by using CRISPR/Cas9 technology were growth normal, but showed blunt shape, and increased basal insulin secretion. Combined proteomics and glycoproteomics demonstrated that G14KO altered cell-to-cell junctions, communication, and adhesion. Insulin receptor (IR) and IGF1-1R were indirectly confirmed for GALNT14 substrates, contributed to diminished IGF1-induced p-AKT levels and cell growth in G14KO cells. Overall, this study uncovers that GALNT14 is a novel modulator in regulating β cells biology, providing a missing link of β cells O-glycosylation to diabetes development.</p></div>","PeriodicalId":18707,"journal":{"name":"Molecular and Cellular Endocrinology","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2024-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140961758","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
17β-estradiol induces hyperresponsiveness in guinea pig airway smooth muscle by inhibiting the plasma membrane Ca2+-ATPase 17β-雌二醇通过抑制质膜 Ca2+-ATP 酶诱导豚鼠气道平滑肌的高反应性。
IF 4.1 3区 医学 Q1 Biochemistry, Genetics and Molecular Biology Pub Date : 2024-05-18 DOI: 10.1016/j.mce.2024.112273
Bianca S. Romero-Martínez , Edgar Flores-Soto , Bettina Sommer , Jorge Reyes-García , David Arredondo-Zamarripa , Héctor Solís-Chagoyán , Cristina Lemini , Nadia A. Rivero-Segura , José A. Santiago-de-la- Cruz , Carlos Pérez-Plascencia , Luis M. Montaño

High serum estrogen concentrations are associated with asthma development and severity, suggesting a link between estradiol and airway hyperresponsiveness (AHR). 17β-estradiol (E2) has non-genomic effects via Ca2+ regulatory mechanisms; however, its effect on the plasma membrane Ca2+-ATPases (PMCA1 and 4) and sarcoplasmic reticulum Ca2+-ATPase (SERCA) is unknown. Hence, in the present study, we aim to demonstrate if E2 favors AHR by increasing intracellular Ca2+ concentrations in guinea pig airway smooth muscle (ASM) through a mechanism involving Ca2+-ATPases.

In guinea pig ASM, Ca2+ microfluorometry, muscle contraction, and Western blot were evaluated. Then, we performed molecular docking analysis between the estrogens and Ca2+ ATPases.

In tracheal rings, E2 produced AHR to carbachol. In guinea pig myocytes, acute exposure to physiological levels of E2 modified the transient Ca2+ peak induced by caffeine to a Ca2+ plateau. The incubation with PMCA inhibitors (lanthanum and carboxyeosin, CE) partially reversed the E2-induced sustained plateau in the caffeine response. In contrast, cyclopiazonic acid (SERCA inhibitor), U-0126 (an inhibitor of ERK 1/2), and choline chloride did not modify the Ca2+ plateau produced by E2. The mitochondrial uniporter activity and the capacitative Ca2+ entry were unaffected by E2. In guinea pig ASM, Western blot analysis demonstrated PMCA1 and PMCA4 expression. The results from the docking modeling demonstrate that E2 binds to both plasma membrane ATPases. In guinea pig tracheal smooth muscle, inhibiting the PMCA with CE, induced hyperresponsiveness to carbachol. 17β-estradiol produces hyperresponsiveness by inhibiting the PMCA in the ASM and could be one of the mechanisms responsible for the increase in asthmatic crisis in women.

高血清雌激素浓度与哮喘的发生和严重程度有关,这表明雌二醇与气道高反应性(AHR)之间存在联系。17β-雌二醇(E2)通过 Ca2+ 调节机制产生非基因组效应;然而,它对质膜 Ca2+-ATP 酶(PMCA1 和 4)和肌浆网 Ca2+-ATP 酶(SERCA)的影响尚不清楚。因此,在本研究中,我们旨在证明 E2 是否会通过 Ca2+-ATP 酶参与的机制增加豚鼠气道平滑肌(ASM)细胞内 Ca2+ 浓度,从而促进 AHR。然后,我们进行了雌激素与 Ca2+ ATP 酶之间的分子对接分析。在豚鼠心肌细胞中,急性暴露于生理水平的E2会将咖啡因诱导的瞬时Ca2+峰值改变为Ca2+高原。与 PMCA 抑制剂(镧和羧基肌苷,CE)一起孵育可部分逆转 E2 诱导的咖啡因反应中的持续高原。相比之下,环噻唑啉酸(SERCA 抑制剂)、U-0126(ERK 1/2抑制剂)和氯化胆碱没有改变 E2 产生的 Ca2+ 高原。线粒体单端口活性和电容性 Ca2+ 进入不受 E2 的影响。在豚鼠 ASM 中,Western 印迹分析显示了 PMCA1 和 PMCA4 的表达。对接模型的结果表明,E2 能与这两种质膜 ATP 酶结合。在豚鼠气管平滑肌中,用 CE 抑制 PMCA 会引起对卡巴胆碱的高反应性。17β-estradiol 通过抑制气管平滑肌中的 PMCA 产生高反应性,这可能是导致女性哮喘危象增加的机制之一。
{"title":"17β-estradiol induces hyperresponsiveness in guinea pig airway smooth muscle by inhibiting the plasma membrane Ca2+-ATPase","authors":"Bianca S. Romero-Martínez ,&nbsp;Edgar Flores-Soto ,&nbsp;Bettina Sommer ,&nbsp;Jorge Reyes-García ,&nbsp;David Arredondo-Zamarripa ,&nbsp;Héctor Solís-Chagoyán ,&nbsp;Cristina Lemini ,&nbsp;Nadia A. Rivero-Segura ,&nbsp;José A. Santiago-de-la- Cruz ,&nbsp;Carlos Pérez-Plascencia ,&nbsp;Luis M. Montaño","doi":"10.1016/j.mce.2024.112273","DOIUrl":"10.1016/j.mce.2024.112273","url":null,"abstract":"<div><p>High serum estrogen concentrations are associated with asthma development and severity, suggesting a link between estradiol and airway hyperresponsiveness (AHR). 17β-estradiol (E2) has non-genomic effects via Ca<sup>2+</sup> regulatory mechanisms; however, its effect on the plasma membrane Ca<sup>2+</sup>-ATPases (PMCA1 and 4) and sarcoplasmic reticulum Ca<sup>2+</sup>-ATPase (SERCA) is unknown. Hence, in the present study, we aim to demonstrate if E2 favors AHR by increasing intracellular Ca<sup>2+</sup> concentrations in guinea pig airway smooth muscle (ASM) through a mechanism involving Ca<sup>2+</sup>-ATPases.</p><p>In guinea pig ASM, Ca<sup>2+</sup> microfluorometry, muscle contraction, and Western blot were evaluated. Then, we performed molecular docking analysis between the estrogens and Ca<sup>2+</sup> ATPases.</p><p>In tracheal rings, E2 produced AHR to carbachol. In guinea pig myocytes, acute exposure to physiological levels of E2 modified the transient Ca<sup>2+</sup> peak induced by caffeine to a Ca<sup>2+</sup> plateau. The incubation with PMCA inhibitors (lanthanum and carboxyeosin, CE) partially reversed the E2-induced sustained plateau in the caffeine response. In contrast, cyclopiazonic acid (SERCA inhibitor), U-0126 (an inhibitor of ERK 1/2), and choline chloride did not modify the Ca<sup>2+</sup> plateau produced by E2. The mitochondrial uniporter activity and the capacitative Ca<sup>2+</sup> entry were unaffected by E2. In guinea pig ASM, Western blot analysis demonstrated PMCA1 and PMCA4 expression. The results from the docking modeling demonstrate that E2 binds to both plasma membrane ATPases. In guinea pig tracheal smooth muscle, inhibiting the PMCA with CE, induced hyperresponsiveness to carbachol. 17β-estradiol produces hyperresponsiveness by inhibiting the PMCA in the ASM and could be one of the mechanisms responsible for the increase in asthmatic crisis in women.</p></div>","PeriodicalId":18707,"journal":{"name":"Molecular and Cellular Endocrinology","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2024-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140961761","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Cellular landscape of adrenocortical carcinoma at single-nuclei resolution 单核分辨率的肾上腺皮质癌细胞图谱。
IF 4.1 3区 医学 Q1 Biochemistry, Genetics and Molecular Biology Pub Date : 2024-05-15 DOI: 10.1016/j.mce.2024.112272
David S. Tourigny , Barbara Altieri , Kerim A. Secener , Silviu Sbiera , Marc P. Schauer , Panagiota Arampatzi , Sabine Herterich , Sascha Sauer , Martin Fassnacht , Cristina L. Ronchi

Adrenocortical carcinoma (ACC) is a rare yet devastating tumour of the adrenal gland with a molecular pathology that remains incompletely understood. To gain novel insights into the cellular landscape of ACC, we generated single-nuclei RNA sequencing (snRNA-seq) data sets from twelve ACC tumour samples and analysed these alongside snRNA-seq data sets from normal adrenal glands (NAGs). We find the ACC tumour microenvironment to be relatively devoid of immune cells compared to NAG tissues, consistent with known high tumour purity values for ACC as an immunologically “cold” tumour. Our analysis identifies three separate groups of ACC samples that are characterised by different relative compositions of adrenocortical cell types. These include cell populations that are specifically enriched in the most clinically aggressive and hormonally active tumours, displaying hallmarks of reorganised cell mechanobiology and dysregulated steroidogenesis, respectively. We also identified and validated a population of mitotically active adrenocortical cells that strongly overexpress genes POLQ, DIAPH3 and EZH2 to support tumour expansion alongside an LGR4+ progenitor-like or cell-of-origin candidate for adrenocortical carcinogenesis. Trajectory inference suggests the fate adopted by malignant adrenocortical cells upon differentiation is associated with the copy number or allelic balance state of the imprinted DLK1/MEG3 genomic locus, which we verified by assessing bulk tumour DNA methylation status. In conclusion, our results therefore provide new insights into the clinical and cellular heterogeneity of ACC, revealing how genetic perturbations to healthy adrenocortical renewal and zonation provide a molecular basis for disease pathogenesis.

肾上腺皮质癌(ACC)是一种罕见的、破坏性极大的肾上腺肿瘤,其分子病理学至今仍不完全清楚。为了深入了解 ACC 的细胞结构,我们从 12 个 ACC 肿瘤样本中生成了单核 RNA 测序(snRNA-seq)数据集,并将这些数据集与正常肾上腺(NAG)的 snRNA-seq 数据集进行了分析。我们发现,与正常肾上腺组织相比,ACC 肿瘤微环境中的免疫细胞相对较少,这与已知的 ACC 作为免疫 "冷 "肿瘤的高肿瘤纯度值相一致。我们的分析确定了肾上腺皮质细胞类型相对组成不同的三组独立的 ACC 样本。其中包括临床侵袭性最强和激素分泌最活跃的肿瘤中特别富集的细胞群,它们分别显示出细胞机械生物学重组和类固醇生成失调的特征。我们还发现并验证了有丝分裂活跃的肾上腺皮质细胞群,这些细胞群强烈过表达基因 POLQ、DIAPH3 和 EZH2,支持肿瘤的扩展,同时也是肾上腺皮质癌变的 LGR4+祖细胞样或起源细胞候选者。轨迹推断表明,恶性肾上腺皮质细胞分化后的命运与印记 DLK1/MEG3 基因组位点的拷贝数或等位基因平衡状态有关,我们通过评估肿瘤大体 DNA 甲基化状态验证了这一点。总之,我们的研究结果为了解 ACC 的临床和细胞异质性提供了新的视角,揭示了健康肾上腺皮质更新和分区的遗传扰动是如何为疾病的发病机制提供分子基础的。
{"title":"Cellular landscape of adrenocortical carcinoma at single-nuclei resolution","authors":"David S. Tourigny ,&nbsp;Barbara Altieri ,&nbsp;Kerim A. Secener ,&nbsp;Silviu Sbiera ,&nbsp;Marc P. Schauer ,&nbsp;Panagiota Arampatzi ,&nbsp;Sabine Herterich ,&nbsp;Sascha Sauer ,&nbsp;Martin Fassnacht ,&nbsp;Cristina L. Ronchi","doi":"10.1016/j.mce.2024.112272","DOIUrl":"10.1016/j.mce.2024.112272","url":null,"abstract":"<div><p>Adrenocortical carcinoma (ACC) is a rare yet devastating tumour of the adrenal gland with a molecular pathology that remains incompletely understood. To gain novel insights into the cellular landscape of ACC, we generated single-nuclei RNA sequencing (snRNA-seq) data sets from twelve ACC tumour samples and analysed these alongside snRNA-seq data sets from normal adrenal glands (NAGs). We find the ACC tumour microenvironment to be relatively devoid of immune cells compared to NAG tissues, consistent with known high tumour purity values for ACC as an immunologically “cold” tumour. Our analysis identifies three separate groups of ACC samples that are characterised by different relative compositions of adrenocortical cell types. These include cell populations that are specifically enriched in the most clinically aggressive and hormonally active tumours, displaying hallmarks of reorganised cell mechanobiology and dysregulated steroidogenesis, respectively. We also identified and validated a population of mitotically active adrenocortical cells that strongly overexpress genes <em>POLQ</em>, <em>DIAPH3</em> and <em>EZH2</em> to support tumour expansion alongside an <em>LGR4</em>+ progenitor-like or cell-of-origin candidate for adrenocortical carcinogenesis. Trajectory inference suggests the fate adopted by malignant adrenocortical cells upon differentiation is associated with the copy number or allelic balance state of the imprinted <em>DLK1</em>/<em>MEG3</em> genomic locus, which we verified by assessing bulk tumour DNA methylation status. In conclusion, our results therefore provide new insights into the clinical and cellular heterogeneity of ACC, revealing how genetic perturbations to healthy adrenocortical renewal and zonation provide a molecular basis for disease pathogenesis.</p></div>","PeriodicalId":18707,"journal":{"name":"Molecular and Cellular Endocrinology","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2024-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S030372072400128X/pdfft?md5=372202bc649f98fce6d7a305da2daa9d&pid=1-s2.0-S030372072400128X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140958581","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
期刊
Molecular and Cellular Endocrinology
全部 Acc. Chem. Res. ACS Applied Bio Materials ACS Appl. Electron. Mater. ACS Appl. Energy Mater. ACS Appl. Mater. Interfaces ACS Appl. Nano Mater. ACS Appl. Polym. Mater. ACS BIOMATER-SCI ENG ACS Catal. ACS Cent. Sci. ACS Chem. Biol. ACS Chemical Health & Safety ACS Chem. Neurosci. ACS Comb. Sci. ACS Earth Space Chem. ACS Energy Lett. ACS Infect. Dis. ACS Macro Lett. ACS Mater. Lett. ACS Med. Chem. Lett. ACS Nano ACS Omega ACS Photonics ACS Sens. ACS Sustainable Chem. Eng. ACS Synth. Biol. Anal. Chem. BIOCHEMISTRY-US Bioconjugate Chem. BIOMACROMOLECULES Chem. Res. Toxicol. Chem. Rev. Chem. Mater. CRYST GROWTH DES ENERG FUEL Environ. Sci. Technol. Environ. Sci. Technol. Lett. Eur. J. Inorg. Chem. IND ENG CHEM RES Inorg. Chem. J. Agric. Food. Chem. J. Chem. Eng. Data J. Chem. Educ. J. Chem. Inf. Model. J. Chem. Theory Comput. J. Med. Chem. J. Nat. Prod. J PROTEOME RES J. Am. Chem. Soc. LANGMUIR MACROMOLECULES Mol. Pharmaceutics Nano Lett. Org. Lett. ORG PROCESS RES DEV ORGANOMETALLICS J. Org. Chem. J. Phys. Chem. J. Phys. Chem. A J. Phys. Chem. B J. Phys. Chem. C J. Phys. Chem. Lett. Analyst Anal. Methods Biomater. Sci. Catal. Sci. Technol. Chem. Commun. Chem. Soc. Rev. CHEM EDUC RES PRACT CRYSTENGCOMM Dalton Trans. Energy Environ. Sci. ENVIRON SCI-NANO ENVIRON SCI-PROC IMP ENVIRON SCI-WAT RES Faraday Discuss. Food Funct. Green Chem. Inorg. Chem. Front. Integr. Biol. J. Anal. At. Spectrom. J. Mater. Chem. A J. Mater. Chem. B J. Mater. Chem. C Lab Chip Mater. Chem. Front. Mater. Horiz. MEDCHEMCOMM Metallomics Mol. Biosyst. Mol. Syst. Des. Eng. Nanoscale Nanoscale Horiz. Nat. Prod. Rep. New J. Chem. Org. Biomol. Chem. Org. Chem. Front. PHOTOCH PHOTOBIO SCI PCCP Polym. Chem.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1