Journal of pharmacological sciences最新文献

英文中文

Efficacy and safety of daprodustat versus darbepoetin alfa in the treatment of anemia in chronic renal failure: Systematic review and meta-analysis of randomized controlled trials

IF 3 3区医学 Q2 PHARMACOLOGY & PHARMACY

Journal of pharmacological sciences

Pub Date : 2025-03-15 DOI: 10.1016/j.jphs.2025.03.006

Shuyue Pang , Zhongtian Wang , Yanyan Fu , Xu Huang

Objectives

To compare the efficacy and safety of daprodustat (DPD) versus darbepoetin alfa (DBPA) in patients with anemia in chronic renal failure.

Materials and methods

Randomized controlled trials (RCTs) of DPD and DBPA in anemia were retrieved from PubMed, Embase, Cochrane library, and Web of Science from inception to August 1, 2023. The collected data were analyzed using Stata 15.0.

Results

Four RCTs involving 7419 patients (3717 in the DPD group and 3702 in the DBPA group) were included in the study. Meta-analysis revealed that there were no significant differences in the change in hemoglobin level [Standardized Mean Difference (SMD) = 3.23, 95 % CI (−0.25, 6.70)], transferrin saturation [SMD = −0.07, 95 % CI (−0.31, 0.17)], total iron [SMD = 0.24, 95 % CI (−0.05, 0.53))], and incidence of adverse events [ RR = 1.02, 95 % CI (0.98, 1.06)] between the two groups. However, DPD was superior in lowering ferritin level [SMD = −0.05, 95 % CI (−0.10, −0.01)] and improving total iron-binding capacity [SMD = 0.57, 95 % CI (0.46, 0.68)] than DBPA.

Conclusions

DPD is not inferior to DBPA in the treatment of anemia in chronic renal failure.

{"title":"Efficacy and safety of daprodustat versus darbepoetin alfa in the treatment of anemia in chronic renal failure: Systematic review and meta-analysis of randomized controlled trials","authors":"Shuyue Pang , Zhongtian Wang , Yanyan Fu , Xu Huang","doi":"10.1016/j.jphs.2025.03.006","DOIUrl":"10.1016/j.jphs.2025.03.006","url":null,"abstract":"<div><h3>Objectives</h3><div>To compare the efficacy and safety of daprodustat (DPD) versus darbepoetin alfa (DBPA) in patients with anemia in chronic renal failure.</div></div><div><h3>Materials and methods</h3><div>Randomized controlled trials (RCTs) of DPD and DBPA in anemia were retrieved from PubMed, Embase, Cochrane library, and Web of Science from inception to August 1, 2023. The collected data were analyzed using Stata 15.0.</div></div><div><h3>Results</h3><div>Four RCTs involving 7419 patients (3717 in the DPD group and 3702 in the DBPA group) were included in the study. Meta-analysis revealed that there were no significant differences in the change in hemoglobin level [Standardized Mean Difference (SMD) = 3.23, 95 % CI (−0.25, 6.70)], transferrin saturation [SMD = −0.07, 95 % CI (−0.31, 0.17)], total iron [SMD = 0.24, 95 % CI (−0.05, 0.53))], and incidence of adverse events [ RR = 1.02, 95 % CI (0.98, 1.06)] between the two groups. However, DPD was superior in lowering ferritin level [SMD = −0.05, 95 % CI (−0.10, −0.01)] and improving total iron-binding capacity [SMD = 0.57, 95 % CI (0.46, 0.68)] than DBPA.</div></div><div><h3>Conclusions</h3><div>DPD is not inferior to DBPA in the treatment of anemia in chronic renal failure.</div></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"158 1","pages":"Pages 68-75"},"PeriodicalIF":3.0,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143642136","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

Ca2+ microdomains in vascular smooth muscle cells: Roles in vascular tone regulation and hypertension

IF 3 3区医学 Q2 PHARMACOLOGY & PHARMACY

Journal of pharmacological sciences

Pub Date : 2025-03-14 DOI: 10.1016/j.jphs.2025.03.008

Yoshiaki Suzuki

Vascular smooth muscle cells (VSMCs) modulate blood pressure by adjusting vascular contractility. Specific families of ion channels that are expressed in VSMCs regulate membrane potential and intracellular Ca²⁺ concentration ([Ca²⁺]_cyt). Subsets of them are known to form molecular complexes with Ca²⁺-sensitive molecules via scaffolding proteins such as caveolin and junctophilin. This enables localized and molecular complex-specific signal transduction to regulate vascular contractility. This intracellular region is referred to as a Ca²⁺ microdomain. When hypertensive stimuli are applied to blood vessels, gene expression of ion channels and scaffold proteins in vascular cells changes dramatically, often leading to membrane depolarization and increased [Ca²⁺]_cyt. As a result, blood vessels undergo functional remodeling characterized by enhanced contractility. In addition, the transcription of inflammatory genes in vascular cells is also upregulated. This induces leukocyte infiltration into the vascular wall and structural remodeling mediated by VSMC proliferation and extracellular matrix remodeling. This functional and structural remodeling perpetuates the hypertensive state, leading to progressive damage to systemic organs. This review summarizes recent findings on the mechanisms by which Ca²⁺ microdomains in VSMCs regulate contractility. In addition, the changes in Ca²⁺ microdomains due to hypertensive stimuli and their contributions to both functional and structural remodeling are summarized.

{"title":"Ca2+ microdomains in vascular smooth muscle cells: Roles in vascular tone regulation and hypertension","authors":"Yoshiaki Suzuki","doi":"10.1016/j.jphs.2025.03.008","DOIUrl":"10.1016/j.jphs.2025.03.008","url":null,"abstract":"<div><div>Vascular smooth muscle cells (VSMCs) modulate blood pressure by adjusting vascular contractility. Specific families of ion channels that are expressed in VSMCs regulate membrane potential and intracellular Ca<sup>2+</sup> concentration ([Ca<sup>2+</sup>]<sub>cyt</sub>). Subsets of them are known to form molecular complexes with Ca<sup>2+</sup>-sensitive molecules via scaffolding proteins such as caveolin and junctophilin. This enables localized and molecular complex-specific signal transduction to regulate vascular contractility. This intracellular region is referred to as a Ca<sup>2+</sup> microdomain. When hypertensive stimuli are applied to blood vessels, gene expression of ion channels and scaffold proteins in vascular cells changes dramatically, often leading to membrane depolarization and increased [Ca<sup>2+</sup>]<sub>cyt</sub>. As a result, blood vessels undergo functional remodeling characterized by enhanced contractility. In addition, the transcription of inflammatory genes in vascular cells is also upregulated. This induces leukocyte infiltration into the vascular wall and structural remodeling mediated by VSMC proliferation and extracellular matrix remodeling. This functional and structural remodeling perpetuates the hypertensive state, leading to progressive damage to systemic organs. This review summarizes recent findings on the mechanisms by which Ca<sup>2+</sup> microdomains in VSMCs regulate contractility. In addition, the changes in Ca<sup>2+</sup> microdomains due to hypertensive stimuli and their contributions to both functional and structural remodeling are summarized.</div></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"158 1","pages":"Pages 59-67"},"PeriodicalIF":3.0,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143642135","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

Wireless recording and autoencoder denoising of intestinal activity in freely moving rats

IF 3 3区医学 Q2 PHARMACOLOGY & PHARMACY

Journal of pharmacological sciences

Pub Date : 2025-03-11 DOI: 10.1016/j.jphs.2025.03.005

Yamato Ishii , Nobuyoshi Matsumoto , Yuji Ikegaya , Tetsuhiko Kashima

Conventional wired systems for recording intestinal motility using strain-gauge transducers physically limit animal movement and are not ideal for long-term studies. Here, we developed a wireless recording system that allows continuous monitoring of intestinal activity in freely moving rats. We also developed a denoising autoencoder that isolates intestinal motility signals from locomotor noise while maintaining a 10-s temporal resolution. The refined data revealed decreased intestinal motility while the rats were behaviorally active. This system has broad applications for in vivo physiological research.

引用次数: 0

The anti-angiogenic effects of arctigenin on choroidal neovascularization pathogenesis

IF 3 3区医学 Q2 PHARMACOLOGY & PHARMACY

Journal of pharmacological sciences

Pub Date : 2025-03-07 DOI: 10.1016/j.jphs.2025.03.003

Aimi Shirakawa , Hiroto Yasuda , Shinsuke Nakamura , Yuichi Takajo , Satoshi Inamasu , Satoshi Yomoda , Shimpei Watanabe , Yoshiki Kuse , Masamitsu Shimazawa

Neovascular age-related macular degeneration (nAMD) is an ocular disease characterized by choroidal neovascularization (CNV), resulting in severe visual impairment. Arctigenin is a natural lignan compound from Arctium lappa L. and has anti-inflammatory and vascular normalizing effects. Here, we investigated the anti-angiogenic effects of arctigenin on CNV formation. Laser-induced CNV model mice were orally administered arctigenin at 100 mg/kg once a day for 5 days before laser irradiation. Oral administration of arctigenin suppressed CNV formation, vascular leakage, and the proliferation of endothelial cells in the CNV lesions. Treatment with arctigenin at 30 μM attenuated vascular endothelial growth factor (VEGF)-induced cell proliferation of human retinal microvascular endothelial cells (HRMECs). Moreover, arctigenin suppressed the phosphorylation of Src, which is involved in VEGF signaling. Arctigenin also inhibited VEGF-induced mitochondrial respiratory activation. These findings suggested that daily intake of arctigenin may have beneficial effects on nAMD.

{"title":"The anti-angiogenic effects of arctigenin on choroidal neovascularization pathogenesis","authors":"Aimi Shirakawa , Hiroto Yasuda , Shinsuke Nakamura , Yuichi Takajo , Satoshi Inamasu , Satoshi Yomoda , Shimpei Watanabe , Yoshiki Kuse , Masamitsu Shimazawa","doi":"10.1016/j.jphs.2025.03.003","DOIUrl":"10.1016/j.jphs.2025.03.003","url":null,"abstract":"<div><div>Neovascular age-related macular degeneration (nAMD) is an ocular disease characterized by choroidal neovascularization (CNV), resulting in severe visual impairment. Arctigenin is a natural lignan compound from <em>Arctium lappa</em> L. and has anti-inflammatory and vascular normalizing effects. Here, we investigated the anti-angiogenic effects of arctigenin on CNV formation. Laser-induced CNV model mice were orally administered arctigenin at 100 mg/kg once a day for 5 days before laser irradiation. Oral administration of arctigenin suppressed CNV formation, vascular leakage, and the proliferation of endothelial cells in the CNV lesions. Treatment with arctigenin at 30 μM attenuated vascular endothelial growth factor (VEGF)-induced cell proliferation of human retinal microvascular endothelial cells (HRMECs). Moreover, arctigenin suppressed the phosphorylation of Src, which is involved in VEGF signaling. Arctigenin also inhibited VEGF-induced mitochondrial respiratory activation. These findings suggested that daily intake of arctigenin may have beneficial effects on nAMD.</div></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"158 1","pages":"Pages 42-51"},"PeriodicalIF":3.0,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143601510","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

Puerarin improves MASLD by remodeling intestinal microenvironment to promote mitochondrial fusion and autophagy

IF 3 3区医学 Q2 PHARMACOLOGY & PHARMACY

Journal of pharmacological sciences

Pub Date : 2025-03-04 DOI: 10.1016/j.jphs.2025.03.001

Chunbin Sun , Mei Du , Shuang Sha , Si Wang , Lei Li , Jiong Hou , Li Li , Jiali Yuan , Jinyuan Yan , Zhongshan Yang

Pueraria Mirifica (Willd. Ohwi) is a medicine with anti-inflammatory and lipid-lowering properties. Puerarin is one of the main active components of Pueraria. The aim of this study was to investigate the possible mechanisms of Pueraria in the treatment of non-alcoholic fatty liver disease. The therapeutic effect of the drug was demonstrated by serum and liver pathology indicators. The mechanism of action of puerarin was demonstrated by intestinal microbial changes and short-chain fatty acid content tests. The mechanism of puerarin alleviating Metabolic dysfunction-associated steatotic liver disease (MASLD) by regulating intestinal flora was predicted by bioinformatics. The relationship between flora and liver was revealed by q-PCR detection of mRNA expression level of liver metabolic genes. And the mechanism of puerarin action was further verified by intestinal microbial clearance experiments. Puerarin reduced vacuolar-like changes, lipid deposition, and inflammatory cell infiltration in the livers of high-fat diet (HFD) model mice. The gut microbiota abundance and diversity were remodeled, short-chain fatty acid content was increased, and the intestinal mucosal barrier was repaired, accompanied by a reduction in inflammatory cytokines. Puerarin regulated mRNA expression of hepatic lipid metabolism genes to alleviate MASLD. These results suggested that puerarin treats MASLD by treating altering bacterial metabolism and anti-inflammation.

{"title":"Puerarin improves MASLD by remodeling intestinal microenvironment to promote mitochondrial fusion and autophagy","authors":"Chunbin Sun , Mei Du , Shuang Sha , Si Wang , Lei Li , Jiong Hou , Li Li , Jiali Yuan , Jinyuan Yan , Zhongshan Yang","doi":"10.1016/j.jphs.2025.03.001","DOIUrl":"10.1016/j.jphs.2025.03.001","url":null,"abstract":"<div><div>Pueraria Mirifica (Willd. Ohwi) is a medicine with anti-inflammatory and lipid-lowering properties. Puerarin is one of the main active components of Pueraria. The aim of this study was to investigate the possible mechanisms of Pueraria in the treatment of non-alcoholic fatty liver disease. The therapeutic effect of the drug was demonstrated by serum and liver pathology indicators. The mechanism of action of puerarin was demonstrated by intestinal microbial changes and short-chain fatty acid content tests. The mechanism of puerarin alleviating Metabolic dysfunction-associated steatotic liver disease (MASLD) by regulating intestinal flora was predicted by bioinformatics. The relationship between flora and liver was revealed by q-PCR detection of mRNA expression level of liver metabolic genes. And the mechanism of puerarin action was further verified by intestinal microbial clearance experiments. Puerarin reduced vacuolar-like changes, lipid deposition, and inflammatory cell infiltration in the livers of high-fat diet (HFD) model mice. The gut microbiota abundance and diversity were remodeled, short-chain fatty acid content was increased, and the intestinal mucosal barrier was repaired, accompanied by a reduction in inflammatory cytokines. Puerarin regulated mRNA expression of hepatic lipid metabolism genes to alleviate MASLD. These results suggested that puerarin treats MASLD by treating altering bacterial metabolism and anti-inflammation.</div></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"158 1","pages":"Pages 27-41"},"PeriodicalIF":3.0,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143578355","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

Retraction notice to "Polyphyllin I inhibits growth and invasion of cisplatin-resistant gastric cancer cells by partially inhibiting CIP2A/PP2A/Akt signaling axis" [J Pharmacol Sci 137 (2018) 305-312].

IF 3 3区医学 Q2 PHARMACOLOGY & PHARMACY

Journal of pharmacological sciences

Pub Date : 2025-03-04 DOI: 10.1016/j.jphs.2025.02.009

Yunfei Zhang, Ping Huang, Xuewen Liu, Yuchen Xiang, Te Zhang, Yezi Wu, Jiaxin Xu, Zhiting Sun, Weiguo Zhen, Liang Zhang, Yuan Si, Ying Liu

引用次数: 0

Specnuezhenide and ecliptasaponin A from Ligustrum lucidum Ait and Ecliptae Herba improved premature ovarian failure by targeting the ESR1

IF 3 3区医学 Q2 PHARMACOLOGY & PHARMACY

Journal of pharmacological sciences

Pub Date : 2025-02-28 DOI: 10.1016/j.jphs.2025.02.011

Jia Xu , Lei Lei , Ping Li , Zi-Chun Huang , Ying Meng , Bing He , Ji-Lin Kuang

This study was designed to investigate the role of Ligustrum lucidum Ait and Ecliptae Herba on premature ovarian failure (POF) and the underlying mechanisms. In the POF mouse model constructed using cyclophosphamide (CTX), Ligustrum lucidum Ait and Ecliptae Herba increased ovarian index and estradiol (E2) levels and curtailed motility and follicle-stimulating hormone (FSH). Ligustrum lucidum Ait and Ecliptae Herba alleviated ovarian pathological damage in POF mice and promoted the expression of ovarian CD31 and Vascular Endothelial Growth Factor A (VEGFA). Through high-performance liquid chromatography-mass spectrometry (HPLC-MS) and network pharmacology, Specnuezhenide and ecliptasaponin A were identified as the key components of Ligustrum lucidum Ait and Ecliptae Herba in anti-POF action. The important target associated with these components is Estrogen Receptor (ESR) 1. Molecular docking and in vitro experiments showed that Specnuezhenide and ecliptasaponin A can both bind to the ESR protein; knocking down ESR1 inhibited the anti-apoptotic effect of Specnuezhenide and ecliptasaponin A on CTX-induced POF cells. In conclusion, the key components of Ligustrum lucidum Ait and Ecliptae Herba that alleviate POF are Specnuezhenide and ecliptasaponin A, which improve the condition by upregulating ESR1.

{"title":"Specnuezhenide and ecliptasaponin A from Ligustrum lucidum Ait and Ecliptae Herba improved premature ovarian failure by targeting the ESR1","authors":"Jia Xu , Lei Lei , Ping Li , Zi-Chun Huang , Ying Meng , Bing He , Ji-Lin Kuang","doi":"10.1016/j.jphs.2025.02.011","DOIUrl":"10.1016/j.jphs.2025.02.011","url":null,"abstract":"<div><div>This study was designed to investigate the role of <em>Ligustrum lucidum Ait</em> and <em>Ecliptae Herba</em> on premature ovarian failure (POF) and the underlying mechanisms. In the POF mouse model constructed using cyclophosphamide (CTX), <em>Ligustrum lucidum Ait</em> and <em>Ecliptae Herba</em> increased ovarian index and estradiol (E2) levels and curtailed motility and follicle-stimulating hormone (FSH). <em>Ligustrum lucidum Ait</em> and <em>Ecliptae Herba</em> alleviated ovarian pathological damage in POF mice and promoted the expression of ovarian CD31 and Vascular Endothelial Growth Factor A (VEGFA). Through high-performance liquid chromatography-mass spectrometry (HPLC-MS) and network pharmacology, Specnuezhenide and ecliptasaponin A were identified as the key components of <em>Ligustrum lucidum Ait</em> and <em>Ecliptae Herba</em> in anti-POF action. The important target associated with these components is Estrogen Receptor (ESR) 1. Molecular docking and <em>in vitro</em> experiments showed that Specnuezhenide and ecliptasaponin A can both bind to the ESR protein; knocking down ESR1 inhibited the anti-apoptotic effect of Specnuezhenide and ecliptasaponin A on CTX-induced POF cells. In conclusion, the key components of <em>Ligustrum lucidum Ait</em> and <em>Ecliptae Herba</em> that alleviate POF are Specnuezhenide and ecliptasaponin A, which improve the condition by upregulating ESR1.</div></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"158 1","pages":"Pages 13-26"},"PeriodicalIF":3.0,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143578354","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

Possible involvement of α, β-unsaturated carbonyl compounds in ferroptosis induced by the cigarette smoke extract of heated tobacco products in vascular smooth muscle cells

IF 3 3区医学 Q2 PHARMACOLOGY & PHARMACY

Journal of pharmacological sciences

Pub Date : 2025-02-27 DOI: 10.1016/j.jphs.2025.02.010

Takahiro Horinouchi , Yuichi Mazaki , Soichi Miwa

In this study, we aimed to determine the cytotoxic factors involved in ferroptosis induced by nicotine- and tar-free cigarette smoke extract (CSE) from heated tobacco products (HTPs) in vascular smooth muscle cells. CSE decreased mitochondrial metabolic activity and increased lactate dehydrogenase leakage. These cytotoxic effects completely disappeared after removing the carbonyls from the mainstream smoke. α, β-Unsaturated carbonyl compounds (acrolein, methyl vinyl ketone, crotonaldehyde, and methacrolein) in the mainstream smoke of HTPs and CSE caused cell damage, which was inhibited by a ferroptosis inhibitor, UAMC-3203. These results suggest that α, β-unsaturated carbonyl compounds might be involved in CSE-induced ferroptosis.

引用次数: 0

Senescent cardiac fibroblasts-derived extracellular vesicles induced autophagy in cardiac fibroblasts via suppression of ras homolog enriched in brain like 1 衰老的心脏成纤维细胞衍生的细胞外囊泡通过抑制富集在大脑中的类ras同源物1诱导心脏成纤维细胞自噬

IF 3 3区医学 Q2 PHARMACOLOGY & PHARMACY

Journal of pharmacological sciences

Pub Date : 2025-02-24 DOI: 10.1016/j.jphs.2025.02.007

Yusei Fujioka, Kosuke Otani, Muneyoshi Okada, Hideyuki Yamawaki

Cardiac fibroblasts (CFs) play roles in the maintenance of myocardial tissue structure. Cellular senescence is a state of stable cell cycle arrest. We previously reported that extracellular vesicles (EV) secreted by doxorubicin (DOX, 1000 nM)-induced senescent CFs (D10³-EV) caused autophagy in CFs. EV mediate cell-to-cell communication through the transfer of microRNA (miRNA). In this study, we focused on miRNA contained in EV and aimed to elucidate mechanisms underlying the autophagy induction by D10³-EV in CFs. Neonatal rat CFs (NRCFs) were treated with DOX for the induction of cellular senescence. EV were isolated from culture media of NRCFs. miRNA was extracted from the EV and miRNA profiles were analyzed using miRNA-seq. Seven miRNAs were significantly decreased, whereas 14 miRNAs were significantly increased in D10³-EV compared with the vehicle-treated NRCFs-derived EV. Among the target genes of 14 miRNAs, Rhebl1 was identified. D10³-EV significantly increased microtubule-associated protein 1 light chain 3 (LC3)-II/LC3-I and decreased protein expression of Ras homolog enriched in brain like 1 (RHEBL1) in NRCFs. Small interfering RNA against Rhebl1 tended to increase LC3-II/LC3-I. In conclusion, we for the first time revealed that the senescent NRCFs-derived EV induced autophagy in NRCFs via the suppression of RHEBL1 protein.

{"title":"Senescent cardiac fibroblasts-derived extracellular vesicles induced autophagy in cardiac fibroblasts via suppression of ras homolog enriched in brain like 1","authors":"Yusei Fujioka, Kosuke Otani, Muneyoshi Okada, Hideyuki Yamawaki","doi":"10.1016/j.jphs.2025.02.007","DOIUrl":"10.1016/j.jphs.2025.02.007","url":null,"abstract":"<div><div>Cardiac fibroblasts (CFs) play roles in the maintenance of myocardial tissue structure. Cellular senescence is a state of stable cell cycle arrest. We previously reported that extracellular vesicles (EV) secreted by doxorubicin (DOX, 1000 nM)-induced senescent CFs (D10<sup>3</sup>-EV) caused autophagy in CFs. EV mediate cell-to-cell communication through the transfer of microRNA (miRNA). In this study, we focused on miRNA contained in EV and aimed to elucidate mechanisms underlying the autophagy induction by D10<sup>3</sup>-EV in CFs. Neonatal rat CFs (NRCFs) were treated with DOX for the induction of cellular senescence. EV were isolated from culture media of NRCFs. miRNA was extracted from the EV and miRNA profiles were analyzed using miRNA-seq. Seven miRNAs were significantly decreased, whereas 14 miRNAs were significantly increased in D10<sup>3</sup>-EV compared with the vehicle-treated NRCFs-derived EV. Among the target genes of 14 miRNAs, <em>Rhebl1</em> was identified. D10<sup>3</sup>-EV significantly increased microtubule-associated protein 1 light chain 3 (LC3)-II/LC3-I and decreased protein expression of Ras homolog enriched in brain like 1 (RHEBL1) in NRCFs. Small interfering RNA against <em>Rhebl1</em> tended to increase LC3-II/LC3-I. In conclusion, we for the first time revealed that the senescent NRCFs-derived EV induced autophagy in NRCFs via the suppression of RHEBL1 protein.</div></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"158 1","pages":"Pages 1-7"},"PeriodicalIF":3.0,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143529791","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

Midnolin gene expression is enhanced by Gq-coupled muscarinic acetylcholine receptor stimulation in SH-SY5Y human neuroblastoma cells

IF 3 3区医学 Q2 PHARMACOLOGY & PHARMACY

Journal of pharmacological sciences

Pub Date : 2025-02-23 DOI: 10.1016/j.jphs.2025.02.006

Ikuo Norota , Yusuke Zuiki , Ayano Chiba , Mikako Nagashima , Jiro Ogura , Hiroaki Yamaguchi , Kuniaki Ishii , Yutaro Obara

We previously demonstrated that the midnolin gene (MIDN) is a risk factor for Parkinson's disease (PD) in Yamagata and British cohorts, and that neurite outgrowth is abolished by MIDN knockout in PC12 cells. Therefore, drugs that upregulate MIDN may have neurotrophic effects. In this study, acetylcholine increased MIDN promoter activity and gene expression in a concentration-dependent manner in SH-SY5Y cells. These effects were suppressed by atropine and a G_q inhibitor, YM254890, indicating that muscarinic receptor/G_q signaling is required for the induction of MIDN by acetylcholine. Our findings suggest that drugs that upregulate MIDN may have therapeutic potential for PD.

引用次数: 0

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