Pub Date : 2024-10-01DOI: 10.1016/j.yexcr.2024.114273
Manya Yu , Vivian Zhou , Michael D. Pisano, Siegfried Janz, Xing Cui
{"title":"Changes in the immune microenvironment during plasma cell tumor development in the IL6Myc mouse model of human multiple myeloma","authors":"Manya Yu , Vivian Zhou , Michael D. Pisano, Siegfried Janz, Xing Cui","doi":"10.1016/j.yexcr.2024.114273","DOIUrl":"10.1016/j.yexcr.2024.114273","url":null,"abstract":"","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"442 2","pages":"Article 114273"},"PeriodicalIF":3.3,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142380404","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-01DOI: 10.1016/j.yexcr.2024.114274
Changbin Lei , Yanmei Li , Jiafeng Chen , Daibang Nie , Xin Song , Cece Lei , Yiqin Zhou , Wang Wang , Jiuyi Sun
Dysregulated adipokine production is an influencing factor for the homeostatic imbalance of tendons. High levels of serum leptin may be a potential link between increasing adiposity and tendinopathy, while the detailed mechanistic explanation was not well-defined. In this study, we investigated the regulatory role of leptin in the tendon stem/progenitor cells (TSPCs) and the molecular mechanism within, and determined the effect of high levels of leptin on tendon recovery. We demonstrated that leptin reduced the viability of isolated rat TSPCs in a dose-dependent way, accompanied with increased transdifferentiation and altered gene expression of a series of extracellular matrix (ECM) enzymatic modulators. Also, we found that leptin could dose-dependently promote TSPCs senescence, while exhibiting limited effect in apoptotic or autophagic induction. Mechanistic study evidenced that leptin treatment increased the AKT/mTOR signaling activity and elevated the expression of leptin receptor (LEPR) in TSPCs, without marked change in MAPK or STAT5 activation. Further, we confirmed that rapamycin treatment, but not AKT inhibition, effectively reduced the leptin-promoted TSPCs senescence. In a rat model with Achilles wounding, exposure to leptin profoundly delayed tendon healing, which was effectively rescued with rapamycin treatment. Our results suggested that leptin could cause intrinsic cellular deficits in TSPCs and impede tendon repair through the AKT/mTOR signaling pathway. These findings evidenced for an important role of elevated leptin levels in the care of tendinopathy and tendon tears.
{"title":"Leptin promotes tendon stem/progenitor cell senescence through the AKT-mTOR signaling pathway","authors":"Changbin Lei , Yanmei Li , Jiafeng Chen , Daibang Nie , Xin Song , Cece Lei , Yiqin Zhou , Wang Wang , Jiuyi Sun","doi":"10.1016/j.yexcr.2024.114274","DOIUrl":"10.1016/j.yexcr.2024.114274","url":null,"abstract":"<div><div>Dysregulated adipokine production is an influencing factor for the homeostatic imbalance of tendons. High levels of serum leptin may be a potential link between increasing adiposity and tendinopathy, while the detailed mechanistic explanation was not well-defined. In this study, we investigated the regulatory role of leptin in the tendon stem/progenitor cells (TSPCs) and the molecular mechanism within, and determined the effect of high levels of leptin on tendon recovery. We demonstrated that leptin reduced the viability of isolated rat TSPCs in a dose-dependent way, accompanied with increased transdifferentiation and altered gene expression of a series of extracellular matrix (ECM) enzymatic modulators. Also, we found that leptin could dose-dependently promote TSPCs senescence, while exhibiting limited effect in apoptotic or autophagic induction. Mechanistic study evidenced that leptin treatment increased the AKT/mTOR signaling activity and elevated the expression of leptin receptor (LEPR) in TSPCs, without marked change in MAPK or STAT5 activation. Further, we confirmed that rapamycin treatment, but not AKT inhibition, effectively reduced the leptin-promoted TSPCs senescence. In a rat model with Achilles wounding, exposure to leptin profoundly delayed tendon healing, which was effectively rescued with rapamycin treatment. Our results suggested that leptin could cause intrinsic cellular deficits in TSPCs and impede tendon repair through the AKT/mTOR signaling pathway. These findings evidenced for an important role of elevated leptin levels in the care of tendinopathy and tendon tears.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"442 2","pages":"Article 114274"},"PeriodicalIF":3.3,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142406303","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Testicular germ cell tumors have the highest incidence in young men (between 15 and 44 years of age) and its etiology is still unclear, but its emergence on puberty suggests a hormone-dependent mechanism for the development of these tumors and their progression. We previously identified the estrogen receptor ESR1, ESR2, GPER and an isoform of ESR1, the ESR1-36 in human testicular embryonic carcinoma NT2/D1 cells, and the activation of SRC induced by ESR1 and ESR2 in these cells. Therefore, this study aimed to analyze the role of ER in the activation of ERK1/2, and the involvement of SRC and ERK1/2 on proliferation, migration, and invasion of the NT2/D1 cells. Our results showed that the activation of ESR1 (using ESR1-selective agonist PPT) or ESR2 (using ESR2-selective agonist DPN) increased phosphorylation of ERK1/2 in NT2/D1 cells. In the presence of the selective inhibitor for SRC-family kinases PP2, or the MEK specific inhibitor U0126, the effects of 17β-estradiol (E2) or PPT were blocked on proliferation and invasion of NT2/D1 cells. Finally, the proliferation, migration, and invasion of NT2/D1 cells simulated by E2 or ESR2 were also blocked by PP2 and U0126. This study provides novel insights into molecular mechanisms of ER in NT2/D1 cells by demonstrating that ER activates rapid responses molecules, including SRC and ERK1/2, which enhance the tumorigenic potential of testicular cancer cells.
{"title":"Estrogen receptor activates SRC and ERK1/2 and promotes tumorigenesis in human testicular embryonic carcinoma cells NT2/D1","authors":"Carla Macheroni, Deborah Simão Souza, Catarina Segreti Porto, Carolina Meloni Vicente","doi":"10.1016/j.yexcr.2024.114282","DOIUrl":"10.1016/j.yexcr.2024.114282","url":null,"abstract":"<div><div>Testicular germ cell tumors have the highest incidence in young men (between 15 and 44 years of age) and its etiology is still unclear, but its emergence on puberty suggests a hormone-dependent mechanism for the development of these tumors and their progression. We previously identified the estrogen receptor ESR1, ESR2, GPER and an isoform of ESR1, the ESR1-36 in human testicular embryonic carcinoma NT2/D1 cells, and the activation of SRC induced by ESR1 and ESR2 in these cells. Therefore, this study aimed to analyze the role of ER in the activation of ERK1/2, and the involvement of SRC and ERK1/2 on proliferation, migration, and invasion of the NT2/D1 cells. Our results showed that the activation of ESR1 (using ESR1-selective agonist PPT) or ESR2 (using ESR2-selective agonist DPN) increased phosphorylation of ERK1/2 in NT2/D1 cells. In the presence of the selective inhibitor for SRC-family kinases PP2, or the MEK specific inhibitor U0126, the effects of 17β-estradiol (E2) or PPT were blocked on proliferation and invasion of NT2/D1 cells. Finally, the proliferation, migration, and invasion of NT2/D1 cells simulated by E2 or ESR2 were also blocked by PP2 and U0126. This study provides novel insights into molecular mechanisms of ER in NT2/D1 cells by demonstrating that ER activates rapid responses molecules, including SRC and ERK1/2, which enhance the tumorigenic potential of testicular cancer cells.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"442 2","pages":"Article 114282"},"PeriodicalIF":3.3,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142446018","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-01DOI: 10.1016/j.yexcr.2024.114277
Hanqing Luo , Hoshun Chong , Yapeng Wang , Yaxuan Gao , Wei Xie , Dongjin Wang
Background
The proliferation potential of mammalian cardiomyocytes declines markedly shortly after birth. Both long non-coding RNAs (lncRNAs) and mRNAs demonstrate altered expression patterns during cardiac development. However, the role of lncRNAs in the cell cycle arrest of cardiomyocytes remains inadequately understood.
Method
The expression pattern of lncRNAs and mRNAs was analyzed in mouse hearts exhibiting varying regenerative potentials on postnatal days (P) 1, 7, and 28. Weighted correlation network analysis (WGCNA) was employed to elucidate the co-expression relationship between lncRNAs and mRNAs. Protein-protein interaction (PPI) network was built using the STRING database, and hub lncRNAs were identified by CytoHubba. Molecular Complex Detection (MCODE) was used to screen core modules of the PPI network in Cytoscape. Upstream lncRNAs and miRNAs which may regulate mRNAs were predicted using miRTarBase and AnnoLnc2, respectively. Myocardial infarction (MI) was induced by ligation of the left anterior descending coronary artery.
Results
Compared with the P1 heart, 618 mRNAs and 414 lncRNAs displayed.
transcriptional changes in the P7 heart, while 2358 mRNAs and 1290 lncRNAs showed from P7 to P28. Gene Ontology (GO) analysis revealed that module 1 in the both comparisons was enriched in the mitotic cell cycle process. 2810408I11Rik and 2010110K18Rik were identified as hub lncRNAs and their effects on the proliferation of cardiomyocytes were verified in vitro. Additionally, four lncRNA-miRNA-mRNA regulatory axes were predicted to explain the mechanism by which 2810408I11Rik and 2010110K18Rik regulate cardiomyocyte proliferation. Notably, the overexpression of 2810408I11Rik enhances cardiomyocyte proliferation and heart regeneration in the adult heart following MI.
Conclusion
This study systematically analyzed the landscape of lncRNAs and mRNAs at P1, P7, and P28. These findings may enhance our understanding of the framework for heart development and could have significant implications for heart regeneration.
{"title":"Screening lncRNAs essential for cardiomyocyte proliferation by integrative profiling of lncRNAs and mRNAs associated with heart development","authors":"Hanqing Luo , Hoshun Chong , Yapeng Wang , Yaxuan Gao , Wei Xie , Dongjin Wang","doi":"10.1016/j.yexcr.2024.114277","DOIUrl":"10.1016/j.yexcr.2024.114277","url":null,"abstract":"<div><h3>Background</h3><div>The proliferation potential of mammalian cardiomyocytes declines markedly shortly after birth. Both long non-coding RNAs (lncRNAs) and mRNAs demonstrate altered expression patterns during cardiac development. However, the role of lncRNAs in the cell cycle arrest of cardiomyocytes remains inadequately understood.</div></div><div><h3>Method</h3><div>The expression pattern of lncRNAs and mRNAs was analyzed in mouse hearts exhibiting varying regenerative potentials on postnatal days (P) 1, 7, and 28. Weighted correlation network analysis (WGCNA) was employed to elucidate the co-expression relationship between lncRNAs and mRNAs. Protein-protein interaction (PPI) network was built using the STRING database, and hub lncRNAs were identified by CytoHubba. Molecular Complex Detection (MCODE) was used to screen core modules of the PPI network in Cytoscape. Upstream lncRNAs and miRNAs which may regulate mRNAs were predicted using miRTarBase and AnnoLnc2, respectively. Myocardial infarction (MI) was induced by ligation of the left anterior descending coronary artery.</div></div><div><h3>Results</h3><div>Compared with the P1 heart, 618 mRNAs and 414 lncRNAs displayed.</div><div>transcriptional changes in the P7 heart, while 2358 mRNAs and 1290 lncRNAs showed from P7 to P28. Gene Ontology (GO) analysis revealed that module 1 in the both comparisons was enriched in the mitotic cell cycle process. 2810408I11Rik and 2010110K18Rik were identified as hub lncRNAs and their effects on the proliferation of cardiomyocytes were verified in vitro. Additionally, four lncRNA-miRNA-mRNA regulatory axes were predicted to explain the mechanism by which 2810408I11Rik and 2010110K18Rik regulate cardiomyocyte proliferation. Notably, the overexpression of 2810408I11Rik enhances cardiomyocyte proliferation and heart regeneration in the adult heart following MI.</div></div><div><h3>Conclusion</h3><div>This study systematically analyzed the landscape of lncRNAs and mRNAs at P1, P7, and P28. These findings may enhance our understanding of the framework for heart development and could have significant implications for heart regeneration.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"442 2","pages":"Article 114277"},"PeriodicalIF":3.3,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142389132","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-01DOI: 10.1016/j.yexcr.2024.114283
Huang wen Jie , Wang Jie , Ma Jianxiong , Zhang Xin , Xu Runnan , Fu Yijia , Lv Bodong , Huang jie
Background
Peripheral nerve injury can result in penile cavernosal denervation muscle atrophy, a primary factor in nerve injury erectile dysfunction (NED). While acetylcholine (Ach) is integral to erectile function, its role and mechanisms in NED need further exploration.
Objective
To investigate the inhibition of CCMSCs Apoptosis and Protein Degradation Pathway by Ach in NED rat model.
Methods
We investigated changes in Ach secretion and receptor expression in an NED rat model, followed by the evaluation of apoptosis and ubiquitin proteasome activation in hypoxic Cavernous smooth muscle cells (CCMSCs) and their co-cultures with Schwann cells (SWCs), under Ach influence. Further, key pathways in NED were identified via high-throughput sequencing, focusing on the p38/MAPK signaling pathway. We examined gene alterations related to this pathway using hypoxic cell models and employed p38 inhibitors to verify protein changes. Our findings in vitro were then confirmed in the NED rat model.
Results
Nerve injury led to reduced Ach receptors and associated gene expression. Experimentally, Ach was shown to counteract CCMSC apoptosis and muscle protein degradation via the p38/MAPK pathway. Inhibition of the Ach degradation pathway demonstrated a capacity to slow NED progression in vivo.
Discussion and conclusion
Activation of Ach receptors may decelerate denervation-induced cavernosal muscle atrophy, suggesting a potential therapeutic approach for NED. This study highlights the crucial role of the Ach/p38/MAPK axis in the pathophysiology of penis smooth muscle atrophy and its broader implications in managing NED and male erectile dysfunction.
背景周围神经损伤可导致阴茎海绵体神经支配肌肉萎缩，这是神经损伤性勃起功能障碍（NED）的主要因素。尽管乙酰胆碱（Ach）是勃起功能不可或缺的物质，但它在 NED 中的作用和机制仍需进一步探讨。目的研究 Ach 对 NED 大鼠模型中阴茎海绵体肌细胞凋亡和蛋白降解途径的抑制作用。方法我们研究了 NED 大鼠模型中 Ach 分泌和受体表达的变化，然后评估了缺氧海绵平滑肌细胞（CCMSCs）及其与许旺细胞（SWCs）共培养物在 Ach 影响下的凋亡和泛素蛋白酶体激活情况。此外，通过高通量测序确定了 NED 的关键通路，重点是 p38/MAPK 信号通路。我们利用缺氧细胞模型检查了与该通路相关的基因变化，并使用 p38 抑制剂来验证蛋白质变化。结果神经损伤导致 Ach 受体和相关基因表达减少。实验表明，Ach 可通过 p38/MAPK 通路抵消 CCMSC 的凋亡和肌肉蛋白降解。讨论与结论激活 Ach 受体可能会减缓神经支配诱导的海绵体肌萎缩，从而为 NED 提供了一种潜在的治疗方法。这项研究强调了 Ach/p38/MAPK 轴在阴茎平滑肌萎缩的病理生理学中的关键作用，以及它对治疗 NED 和男性勃起功能障碍的广泛影响。
{"title":"Mechanism of denervation muscle atrophy mediated by Ach/p38/MAPK pathway in rats with erectile dysfunction caused by nerve injury","authors":"Huang wen Jie , Wang Jie , Ma Jianxiong , Zhang Xin , Xu Runnan , Fu Yijia , Lv Bodong , Huang jie","doi":"10.1016/j.yexcr.2024.114283","DOIUrl":"10.1016/j.yexcr.2024.114283","url":null,"abstract":"<div><h3>Background</h3><div>Peripheral nerve injury can result in penile cavernosal denervation muscle atrophy, a primary factor in nerve injury erectile dysfunction (NED). While acetylcholine (Ach) is integral to erectile function, its role and mechanisms in NED need further exploration.</div></div><div><h3>Objective</h3><div>To investigate the inhibition of CCMSCs Apoptosis and Protein Degradation Pathway by Ach in NED rat model.</div></div><div><h3>Methods</h3><div>We investigated changes in Ach secretion and receptor expression in an NED rat model, followed by the evaluation of apoptosis and ubiquitin proteasome activation in hypoxic Cavernous smooth muscle cells (CCMSCs) and their co-cultures with Schwann cells (SWCs), under Ach influence. Further, key pathways in NED were identified via high-throughput sequencing, focusing on the p38/MAPK signaling pathway. We examined gene alterations related to this pathway using hypoxic cell models and employed p38 inhibitors to verify protein changes. Our findings in vitro were then confirmed in the NED rat model.</div></div><div><h3>Results</h3><div>Nerve injury led to reduced Ach receptors and associated gene expression. Experimentally, Ach was shown to counteract CCMSC apoptosis and muscle protein degradation via the p38/MAPK pathway. Inhibition of the Ach degradation pathway demonstrated a capacity to slow NED progression in vivo.</div></div><div><h3>Discussion and conclusion</h3><div>Activation of Ach receptors may decelerate denervation-induced cavernosal muscle atrophy, suggesting a potential therapeutic approach for NED. This study highlights the crucial role of the Ach/p38/MAPK axis in the pathophysiology of penis smooth muscle atrophy and its broader implications in managing NED and male erectile dysfunction.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"442 2","pages":"Article 114283"},"PeriodicalIF":3.3,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142441510","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-01DOI: 10.1016/j.yexcr.2024.114280
Jia Zhang , Lina Zhang , Wenzhen Wang , Lin Wang , Xiaolei Liang , Lingyun Wei , Qian Hao , Lili Wang , Xiaochun Liu
Stress urinary incontinence (SUI), characterized by involuntary urine leakage during increased abdominal pressure, remains poorly understood regarding its pathophysiology and treatment. In this study, we utilized single-cell sequencing to analyze the transcriptomic profiles of different cell types in anterior vaginal wall of SUI patients, aiming to explore the heterogeneity of the extracellular matrix (ECM) and immune microenvironment in SUI pathogenesis. Our results identified eleven cell types, including connective tissue cells, immune cells, and glial cells. Specifically, fibroblasts, smooth muscle cells, epithelial cells and T cells displayed transcriptional characteristics highly relevant to SUI pathogenesis. We observed that most cell types participate in ECM metabolism and immune-inflammatory responses, indicating a synergistic role of multiple vaginal cell types in SUI. Furthermore, altered intercellular communication, particularly between fibroblasts and T cells, was noted in SUI. This study provides novel single-cell insights into SUI and identifies potential biomarkers and therapeutic targets for future research.
压力性尿失禁（SUI）的特点是在腹压增加时出现不自主漏尿，但人们对其病理生理学和治疗方法的了解仍然很少。在这项研究中，我们利用单细胞测序技术分析了 SUI 患者阴道前壁不同类型细胞的转录组图谱，旨在探索细胞外基质（ECM）和免疫微环境在 SUI 发病机制中的异质性。我们的研究结果发现了 11 种细胞类型，包括结缔组织细胞、免疫细胞和神经胶质细胞。具体来说，成纤维细胞、平滑肌细胞、上皮细胞和 T 细胞显示出与 SUI 发病机制高度相关的转录特征。我们观察到，大多数细胞类型都参与了 ECM 代谢和免疫炎症反应，这表明多种阴道细胞类型在 SUI 中发挥着协同作用。此外，我们还注意到 SUI 中细胞间通信的改变，尤其是成纤维细胞和 T 细胞之间的通信。这项研究提供了有关 SUI 的单细胞新见解，并为未来研究确定了潜在的生物标记物和治疗目标。
{"title":"Heterogeneity in extracellular matrix and immune microenvironment of anterior vaginal wall revealed by single-cell sequencing in women with stress urinary incontinence","authors":"Jia Zhang , Lina Zhang , Wenzhen Wang , Lin Wang , Xiaolei Liang , Lingyun Wei , Qian Hao , Lili Wang , Xiaochun Liu","doi":"10.1016/j.yexcr.2024.114280","DOIUrl":"10.1016/j.yexcr.2024.114280","url":null,"abstract":"<div><div>Stress urinary incontinence (SUI), characterized by involuntary urine leakage during increased abdominal pressure, remains poorly understood regarding its pathophysiology and treatment. In this study, we utilized single-cell sequencing to analyze the transcriptomic profiles of different cell types in anterior vaginal wall of SUI patients, aiming to explore the heterogeneity of the extracellular matrix (ECM) and immune microenvironment in SUI pathogenesis. Our results identified eleven cell types, including connective tissue cells, immune cells, and glial cells. Specifically, fibroblasts, smooth muscle cells, epithelial cells and T cells displayed transcriptional characteristics highly relevant to SUI pathogenesis. We observed that most cell types participate in ECM metabolism and immune-inflammatory responses, indicating a synergistic role of multiple vaginal cell types in SUI. Furthermore, altered intercellular communication, particularly between fibroblasts and T cells, was noted in SUI. This study provides novel single-cell insights into SUI and identifies potential biomarkers and therapeutic targets for future research.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"442 2","pages":"Article 114280"},"PeriodicalIF":3.3,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142438337","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-01DOI: 10.1016/j.yexcr.2024.114271
Shuaijie Sun , Huijin Li , Shanshan Liu , Xiaojuan Xie , Wen Zhai , Jingjing Pan
Metabolic reprogramming is a hallmark of cancer, and abnormal lipid metabolism is associated with drug resistance in bladder cancer cells. The long noncoding RNA (lncRNA) UCA1 is overexpressed in bladder cancer, but its functional contribution to lipid metabolism remains uncharacterized. In this study, we demonstrated that lncRNA UCA1 inhibits epirubicin-induced cell apoptosis by supporting abnormal lipid metabolism in bladder cancer cells. Mechanistically, lncRNA UCA1 promotes lipid accumulation in vitro and in vivo by upregulating PPARα mRNA and protein expression, which is mediated by miR-30a-3p. Knockdown of lncRNA UCA1 increased epirubicin-induced apoptosis via miR-30a-3p/PPARα and downstream p-AKT/p-GSK-3β/β-catenin signaling. Furthermore, mixed free fatty acids upregulated lncRNA UCA1 expression by promoting recruitment of the transcription factor RXRα to the lncRNA UCA1 promoter. These findings were verified in a mouse xenograft model and are consistent with the expression patterns in human bladder cancer patients. Overall, these findings establish the role of lncRNA UCA1 in lipid metabolism and bladder cancer cell resistance to epirubicin, suggesting that lncRNA UCA1 may serve as a candidate target for enhancing bladder cancer chemotherapy.
{"title":"Long noncoding RNA UCA1 inhibits epirubicin-induced apoptosis by activating PPARα-mediated lipid metabolism","authors":"Shuaijie Sun , Huijin Li , Shanshan Liu , Xiaojuan Xie , Wen Zhai , Jingjing Pan","doi":"10.1016/j.yexcr.2024.114271","DOIUrl":"10.1016/j.yexcr.2024.114271","url":null,"abstract":"<div><div>Metabolic reprogramming is a hallmark of cancer, and abnormal lipid metabolism is associated with drug resistance in bladder cancer cells. The long noncoding RNA (lncRNA) UCA1 is overexpressed in bladder cancer, but its functional contribution to lipid metabolism remains uncharacterized. In this study, we demonstrated that lncRNA UCA1 inhibits epirubicin-induced cell apoptosis by supporting abnormal lipid metabolism in bladder cancer cells. Mechanistically, lncRNA UCA1 promotes lipid accumulation <em>in vitro</em> and <em>in vivo</em> by upregulating PPARα mRNA and protein expression, which is mediated by miR-30a-3p. Knockdown of lncRNA UCA1 increased epirubicin-induced apoptosis via miR-30a-3p/PPARα and downstream p-AKT/p-GSK-3β/β-catenin signaling. Furthermore, mixed free fatty acids upregulated lncRNA UCA1 expression by promoting recruitment of the transcription factor RXRα to the lncRNA UCA1 promoter. These findings were verified in a mouse xenograft model and are consistent with the expression patterns in human bladder cancer patients. Overall, these findings establish the role of lncRNA UCA1 in lipid metabolism and bladder cancer cell resistance to epirubicin, suggesting that lncRNA UCA1 may serve as a candidate target for enhancing bladder cancer chemotherapy.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"442 2","pages":"Article 114271"},"PeriodicalIF":3.3,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142364964","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-01DOI: 10.1016/j.yexcr.2024.114269
Ke Zhang , Wen Luo , Haijun Liu , Jin Gong
Colorectal cancer (CRC) is the third deadliest cancer in the world, with a high incidence, aggressiveness, poor prognosis, and resistant to drugs. 5-fluorouracil (5-FU) is the most commonly used drug for the chemotherapeutic of CRC, however, CRC is resistant to 5-FU after a period of treatment. Therefore, there is an urgent need to explore the underlying molecular mechanisms of CRC resistance to 5-FU. In the present study, we found that the expression of PANX2 was increased in CRC tissues and metastatic tissues from the TCGA database. The K-M survival curve showed that the high expression of PANX2 was associated with poor cancer prognosis. GDSC database showed that the IC50 of 5-Fu in the PANX2 high expression group was significantly higher, and the results were verified in CRC cells. In vitro cell function and in vivo tumorigenesis experiments showed that PANX2 promoted CRC cell proliferation, clone formation, migration and tumorigenesis in vivo. WB result revealed that PANX2 may lead to resistance to 5-Fu in CRC by affecting the PI3K-AKT signaling pathway. Overall, PANX2 regulates CRC proliferation, clone formation, migration, and 5-Fu resistance by PI3K-AKT signaling pathway.
{"title":"PANX2 promotes malignant transformation of colorectal cancer and 5-Fu resistance through PI3K-AKT signaling pathway","authors":"Ke Zhang , Wen Luo , Haijun Liu , Jin Gong","doi":"10.1016/j.yexcr.2024.114269","DOIUrl":"10.1016/j.yexcr.2024.114269","url":null,"abstract":"<div><div>Colorectal cancer (CRC) is the third deadliest cancer in the world, with a high incidence, aggressiveness, poor prognosis, and resistant to drugs. 5-fluorouracil (5-FU) is the most commonly used drug for the chemotherapeutic of CRC, however, CRC is resistant to 5-FU after a period of treatment. Therefore, there is an urgent need to explore the underlying molecular mechanisms of CRC resistance to 5-FU. In the present study, we found that the expression of PANX2 was increased in CRC tissues and metastatic tissues from the TCGA database. The K-M survival curve showed that the high expression of PANX2 was associated with poor cancer prognosis. GDSC database showed that the IC50 of 5-Fu in the PANX2 high expression group was significantly higher, and the results were verified in CRC cells. In vitro cell function and in vivo tumorigenesis experiments showed that PANX2 promoted CRC cell proliferation, clone formation, migration and tumorigenesis in vivo. WB result revealed that PANX2 may lead to resistance to 5-Fu in CRC by affecting the PI3K<strong>-</strong>AKT signaling pathway. Overall, PANX2 regulates CRC proliferation, clone formation, migration, and 5-Fu resistance by PI3K<strong>-</strong>AKT signaling pathway.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"442 2","pages":"Article 114269"},"PeriodicalIF":3.3,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142399868","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-01DOI: 10.1016/j.yexcr.2024.114272
Elsayed G.E. Elsakka , Heba M. Midan , Ahmed I. Abulsoud , Doaa Fathi , Nourhan M. Abdelmaksoud , Sherif S. Abdel Mageed , Mohamed Bakr Zaki , Mai A. Abd-Elmawla , Nehal I. Rizk , Mahmoud A. Elrebehy , Tamer M. Abdelghany , Ahmed E. Elesawy , Reem K. Shahin , Manar Mohammed El Tabaa , Osama A. Mohammed , Mustafa Ahmed Abdel-Reheim , Mohammed S. Elballal , Ahmed S. Doghish
The newly discovered programmed iron-dependent necrosis, ferroptosis, is a novel pathway that is controlled by iron-dependent lipid peroxidation and cellular redox changes. It can be triggered intrinsically by low antioxidant enzyme activity or extrinsically by blocking amino acid transporters or activating iron transporters. The induction of ferroptosis involves the activation of specific proteins, suppression of transporters, and increased endoplasmic reticulum (ER) stress (a condition in which the ER, a crucial organelle involved in protein folding and processing, becomes overwhelmed by an accumulation of misfolded or unfolded proteins. This situation disrupts the normal functioning of the ER, leading to a cellular stress response known as the unfolded protein response), leading to lipid peroxidation byproduct accumulation and toxic reactive oxygen species (ROS), which are highly reactive molecules derived from diatomic oxygen and include various forms such as superoxide (O₂⁻), hydroxyl radicals (•OH), and hydrogen peroxide (H₂O₂). Ferroptosis is closely associated with signaling molecules in lung cancer, including epidermal growth factor receptor (EGFR), mitogen-activated protein kinase (MAPK), hypoxia-inducible factor 1-alpha (HIF-1α), and P53, and is regulated by epigenetic factors such as microRNAs (miRNAs). miRNAs are small non-coding RNA molecules that regulate gene expression by binding to target messenger RNAs (mRNAs), leading to translational repression or degradation. Several miRNAs have been found to modulate ferroptosis by targeting key genes involved in iron metabolism, lipid peroxidation, and antioxidant defense pathways. The research on ferroptosis has expanded to target its role in lung cancer treatment and resistance prevention. This review encapsulates the significance of ferroptosis in lung cancer. Understanding the mechanisms and implications of ferroptosis in lung cancer cells may lead to targeted therapies exploiting cancer cell vulnerabilities to ferroptosis Also, improving treatment outcomes, and overcoming resistance.
{"title":"Emerging insights: miRNA modulation of ferroptosis pathways in lung cancer","authors":"Elsayed G.E. Elsakka , Heba M. Midan , Ahmed I. Abulsoud , Doaa Fathi , Nourhan M. Abdelmaksoud , Sherif S. Abdel Mageed , Mohamed Bakr Zaki , Mai A. Abd-Elmawla , Nehal I. Rizk , Mahmoud A. Elrebehy , Tamer M. Abdelghany , Ahmed E. Elesawy , Reem K. Shahin , Manar Mohammed El Tabaa , Osama A. Mohammed , Mustafa Ahmed Abdel-Reheim , Mohammed S. Elballal , Ahmed S. Doghish","doi":"10.1016/j.yexcr.2024.114272","DOIUrl":"10.1016/j.yexcr.2024.114272","url":null,"abstract":"<div><div>The newly discovered programmed iron-dependent necrosis, ferroptosis, is a novel pathway that is controlled by iron-dependent lipid peroxidation and cellular redox changes. It can be triggered intrinsically by low antioxidant enzyme activity or extrinsically by blocking amino acid transporters or activating iron transporters. The induction of ferroptosis involves the activation of specific proteins, suppression of transporters, and increased endoplasmic reticulum (ER) stress (a condition in which the ER, a crucial organelle involved in protein folding and processing, becomes overwhelmed by an accumulation of misfolded or unfolded proteins. This situation disrupts the normal functioning of the ER, leading to a cellular stress response known as the unfolded protein response), leading to lipid peroxidation byproduct accumulation and toxic reactive oxygen species (ROS), which are highly reactive molecules derived from diatomic oxygen and include various forms such as superoxide (O₂⁻), hydroxyl radicals (•OH), and hydrogen peroxide (H₂O₂). Ferroptosis is closely associated with signaling molecules in lung cancer, including epidermal growth factor receptor (EGFR), mitogen-activated protein kinase (MAPK), hypoxia-inducible factor 1-alpha (HIF-1α), and P53, and is regulated by epigenetic factors such as microRNAs (miRNAs). miRNAs are small non-coding RNA molecules that regulate gene expression by binding to target messenger RNAs (mRNAs), leading to translational repression or degradation. Several miRNAs have been found to modulate ferroptosis by targeting key genes involved in iron metabolism, lipid peroxidation, and antioxidant defense pathways. The research on ferroptosis has expanded to target its role in lung cancer treatment and resistance prevention. This review encapsulates the significance of ferroptosis in lung cancer. Understanding the mechanisms and implications of ferroptosis in lung cancer cells may lead to targeted therapies exploiting cancer cell vulnerabilities to ferroptosis Also, improving treatment outcomes, and overcoming resistance.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"442 2","pages":"Article 114272"},"PeriodicalIF":3.3,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142371407","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Alopecia areata (AA) is a chronic autoimmune disease. Th1/Th2 and Treg/Th17 cells and their cytokines are implicated in AA, and we explored their clinical significance in AA.
Methods
AA patients and healthy people (controls) were enrolled, with their Th1/Th2/Th17/Treg cell proportion changes and serum Th1 (INF-γ)/Th2 (IL-5, IL-6)/Th17 (IL-17, IL-22)/Treg (IL-35) cytokine levels assessed. AA patients were assigned into mild, moderate and severe alopecia according to Severity of Alopecia Tool (SALT). The relationship between alopecia severity and initial onset age, disease course, family/smoking/drinking history and sleep disorders was explored. Th1/Th2 and Treg/Th17 cells and their cytokine levels in AA patients with different severity levels were compared. The correlation between cytokine levels and SALT scores was analyzed using Spearman. Additionally, the changes of serum cytokine levels in inactive/active AA patients were compared.
Results
AA patients differed from controls in family history/smoking history/drinking history/sleep disorders. Peripheral blood Th1/Th2/Th17 cell proportions and INF-γ/IL-5/IL-6/IL-17/IL-22 levels increased, while Treg cell proportions and IL-35 level dropped. With higher alopecia severity, the proportions of Th1, Th2 and Th17 cells increased, and Treg cell proportion decreased. AA patients with mild/moderate alopecia had significant differences in IL-17 level. Serum INF-γ, IL-5, IL-17 and IL-22 levels were elevated, and IL-35 level dropped in severe AA patients versus moderate AA patients.
Conclusion
Th1/Th2/Th17 cell proportions and serum INF-γ/IL-5/IL-6/IL-17/IL-22 levels in AA patients were up-regulated, while Treg cell proportion and IL-35 level were repressed. SALT scores were positively-correlated with serum IL-5/IL-17 levels. SALT scores were negatively-correlated with serum IL-35.
背景资料斑秃（AA）是一种慢性自身免疫性疾病。方法招募AA患者和健康人（对照组），评估他们的Th1/Th2/Th17/Treg细胞比例变化和血清Th1（INF-γ）/Th2（IL-5、IL-6）/Th17（IL-17、IL-22）/Treg（IL-35）细胞因子水平。根据脱发严重程度工具（SALT）将 AA 患者分为轻度、中度和重度脱发。研究还探讨了脱发严重程度与最初发病年龄、病程、家族史/吸烟史/饮酒史和睡眠障碍之间的关系。比较了不同严重程度 AA 患者的 Th1/Th2 和 Treg/Th17 细胞及其细胞因子水平。使用 Spearman 分析了细胞因子水平与 SALT 评分之间的相关性。结果 AAA 患者在家族史/吸烟史/饮酒史/睡眠障碍方面与对照组存在差异。外周血Th1/Th2/Th17细胞比例和INF-γ/IL-5/IL-6/IL-17/IL-22水平升高，而Treg细胞比例和IL-35水平下降。脱发严重程度越高，Th1、Th2 和 Th17 细胞比例越高，Treg 细胞比例越低。轻度/中度脱发的 AA 患者的 IL-17 水平有显著差异。结论AA患者中Th1/Th2/Th17细胞比例和血清INF-γ/IL-5/IL-6/IL-17/IL-22水平上调，而Treg细胞比例和IL-35水平受抑制。SALT 评分与血清 IL-5/IL-17 水平呈正相关。SALT 评分与血清 IL-35 呈负相关。
{"title":"Changes and significance of Th1/Th2 and Treg/Th17 cells and their cytokines in patients with alopecia areata","authors":"Xiaojing Yang , Wei Zhang , Xuming Zhao , Wenli Hou , Yuanhui Wu , Dongmei Feng , Zhaoying Meng , Xiangzhao Zhou","doi":"10.1016/j.yexcr.2024.114259","DOIUrl":"10.1016/j.yexcr.2024.114259","url":null,"abstract":"<div><h3>Background</h3><div>Alopecia areata (AA) is a chronic autoimmune disease. Th1/Th2 and Treg/Th17 cells and their cytokines are implicated in AA, and we explored their clinical significance in AA.</div></div><div><h3>Methods</h3><div>AA patients and healthy people (controls) were enrolled, with their Th1/Th2/Th17/Treg cell proportion changes and serum Th1 (INF-γ)/Th2 (IL-5, IL-6)/Th17 (IL-17, IL-22)/Treg (IL-35) cytokine levels assessed. AA patients were assigned into mild, moderate and severe alopecia according to Severity of Alopecia Tool (SALT). The relationship between alopecia severity and initial onset age, disease course, family/smoking/drinking history and sleep disorders was explored. Th1/Th2 and Treg/Th17 cells and their cytokine levels in AA patients with different severity levels were compared. The correlation between cytokine levels and SALT scores was analyzed using Spearman. Additionally, the changes of serum cytokine levels in inactive/active AA patients were compared.</div></div><div><h3>Results</h3><div>AA patients differed from controls in family history/smoking history/drinking history/sleep disorders. Peripheral blood Th1/Th2/Th17 cell proportions and INF-γ/IL-5/IL-6/IL-17/IL-22 levels increased, while Treg cell proportions and IL-35 level dropped. With higher alopecia severity, the proportions of Th1, Th2 and Th17 cells increased, and Treg cell proportion decreased. AA patients with mild/moderate alopecia had significant differences in IL-17 level. Serum INF-γ, IL-5, IL-17 and IL-22 levels were elevated, and IL-35 level dropped in severe AA patients versus moderate AA patients.</div></div><div><h3>Conclusion</h3><div>Th1/Th2/Th17 cell proportions and serum INF-γ/IL-5/IL-6/IL-17/IL-22 levels in AA patients were up-regulated, while Treg cell proportion and IL-35 level were repressed. SALT scores were positively-correlated with serum IL-5/IL-17 levels. SALT scores were negatively-correlated with serum IL-35.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"442 2","pages":"Article 114259"},"PeriodicalIF":3.3,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142250463","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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