{"title":"由 NR4A1 转录激活的 SOCS3 在盆腔器官脱垂中诱导阴道成纤维细胞凋亡和细胞外基质降解","authors":"Xin Jin, Qing Hu, Meiying Qin, Yitong Yin, Zhijun Xia","doi":"10.4274/balkanmedj.galenos.2023.2023-10-60","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Pelvic organ prolapse (POP) is a common gynecological chronic disorder. Human vaginal fibroblasts (HVFs) that maintain the integrity of vaginal wall tissues are essential for keeping pelvic organs in place. Apoptosis and the degradation of the extracellular matrix in HVFs contribute to the progression of POP. The cytokine signal transduction inhibitor 3 (<i>SOCS3</i>) exerts significant regulatory effects on cell signal transduction pathways, thereby affecting various pathological processes.</p><p><strong>Aims: </strong>To explore the role and mechanism of <i>SOCS3</i> on HVFs in the context of POP.</p><p><strong>Study design: </strong>In vitro cell lines and human-sample study.</p><p><strong>Methods: </strong>Anterior vaginal wall tissues were obtained from POP or non-POP patients for the analysis of <i>SOCS3</i> expression. HVFs were isolated from the vaginal tissues of POP patients, and <i>SOCS3</i> was either overexpressed or knocked down in HVFs via lentivirus infection. Subsequently, the biological function and mechanism of <i>SOCS3</i> in HVFs were investigated.</p><p><strong>Results: </strong><i>SOCS3</i> was highly expressed in the vaginal tissues of POP patients compared to non-POP patients. Functionally, the overexpression of <i>SOCS3</i> suppressed cell viability while promoting cell apoptosis in HVFs. The overexpression of <i>SOCS3</i> also accelerated extracellular matrix degradation (decreasing collagen I, collagen III, and elastin, and increasing <i>MMP2 </i>and <i>MMP9</i>). In terms of mechanism, <i>NR4A1</i> transcriptionally activated <i>SOCS3</i> by binding to its promoter. Furthermore, rescue experiments revealed that <i>SOCS3</i> knockdown hindered <i>NR4A1</i> overexpression-induced cell apoptosis and extracellular matrix degradation in HVFs.</p><p><strong>Conclusion: </strong><i>SOCS3</i> mediated the apoptotic and extracellular matrix degradation effects of <i>NR4A1</i> on HVFs, underlining that the restraining of the <i>SOCS3</i> expression may be a promising strategy for POP treatment.</p>","PeriodicalId":8690,"journal":{"name":"Balkan Medical Journal","volume":null,"pages":null},"PeriodicalIF":1.9000,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10913121/pdf/","citationCount":"0","resultStr":"{\"title\":\"<i>SOCS3</i>, Transcriptionally Activated by <i>NR4A1</i>, Induces Apoptosis and Extracellular Matrix Degradation of Vaginal Fibroblasts in Pelvic Organ Prolapse\",\"authors\":\"Xin Jin, Qing Hu, Meiying Qin, Yitong Yin, Zhijun Xia\",\"doi\":\"10.4274/balkanmedj.galenos.2023.2023-10-60\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Pelvic organ prolapse (POP) is a common gynecological chronic disorder. Human vaginal fibroblasts (HVFs) that maintain the integrity of vaginal wall tissues are essential for keeping pelvic organs in place. Apoptosis and the degradation of the extracellular matrix in HVFs contribute to the progression of POP. The cytokine signal transduction inhibitor 3 (<i>SOCS3</i>) exerts significant regulatory effects on cell signal transduction pathways, thereby affecting various pathological processes.</p><p><strong>Aims: </strong>To explore the role and mechanism of <i>SOCS3</i> on HVFs in the context of POP.</p><p><strong>Study design: </strong>In vitro cell lines and human-sample study.</p><p><strong>Methods: </strong>Anterior vaginal wall tissues were obtained from POP or non-POP patients for the analysis of <i>SOCS3</i> expression. HVFs were isolated from the vaginal tissues of POP patients, and <i>SOCS3</i> was either overexpressed or knocked down in HVFs via lentivirus infection. Subsequently, the biological function and mechanism of <i>SOCS3</i> in HVFs were investigated.</p><p><strong>Results: </strong><i>SOCS3</i> was highly expressed in the vaginal tissues of POP patients compared to non-POP patients. Functionally, the overexpression of <i>SOCS3</i> suppressed cell viability while promoting cell apoptosis in HVFs. The overexpression of <i>SOCS3</i> also accelerated extracellular matrix degradation (decreasing collagen I, collagen III, and elastin, and increasing <i>MMP2 </i>and <i>MMP9</i>). In terms of mechanism, <i>NR4A1</i> transcriptionally activated <i>SOCS3</i> by binding to its promoter. Furthermore, rescue experiments revealed that <i>SOCS3</i> knockdown hindered <i>NR4A1</i> overexpression-induced cell apoptosis and extracellular matrix degradation in HVFs.</p><p><strong>Conclusion: </strong><i>SOCS3</i> mediated the apoptotic and extracellular matrix degradation effects of <i>NR4A1</i> on HVFs, underlining that the restraining of the <i>SOCS3</i> expression may be a promising strategy for POP treatment.</p>\",\"PeriodicalId\":8690,\"journal\":{\"name\":\"Balkan Medical Journal\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":1.9000,\"publicationDate\":\"2024-03-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10913121/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Balkan Medical Journal\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.4274/balkanmedj.galenos.2023.2023-10-60\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/1/17 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q2\",\"JCRName\":\"MEDICINE, GENERAL & INTERNAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Balkan Medical Journal","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.4274/balkanmedj.galenos.2023.2023-10-60","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/1/17 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"MEDICINE, GENERAL & INTERNAL","Score":null,"Total":0}
引用次数: 0
摘要
背景:盆腔器官脱垂(POP)是一种常见的妇科慢性疾病。维持阴道壁组织完整性的人类阴道成纤维细胞(HVFs)对保持盆腔器官的位置至关重要。阴道成纤维细胞的凋亡和细胞外基质(ECM)的降解导致了 POP 的恶化。细胞因子信号转导抑制因子 3(SOCS3)对细胞信号转导通路具有显著的调控作用,从而影响各种病理过程。目的:探讨 SOCS3 在 POP 中对 HVFs 的作用和机制:研究设计:实验研究:方法:从 POP 或非 POP 患者身上获取阴道前壁组织,用于分析 SOCS3 的表达。从 POP 患者的阴道组织中分离出 HVFs,通过慢病毒感染在 HVFs 中过表达或敲除 SOCS3。结果表明:SOCS3在HVFs中高表达:结果:与非 POP 患者相比,SOCS3 在 POP 患者的阴道组织中高表达。在功能上,SOCS3 的过表达抑制了 HVFs 中细胞的活力,同时促进了细胞的凋亡。过表达 SOCS3 还会加速 ECM 降解(减少胶原蛋白 I、胶原蛋白 III 和弹性蛋白,增加 MMP2 和 MMP9)。在机制方面,NR4A1 通过与其启动子结合转录激活了 SOCS3。此外,拯救实验表明,敲除 SOCS3 会阻碍 NR4A1 过表达诱导的 HVFs 细胞凋亡和 ECM 降解:结论:SOCS3 介导了 NR4A1 对 HVFs 的细胞凋亡和 ECM 降解作用,这表明抑制 SOCS3 的表达可能是治疗持久性有机污染物的一种有效策略。
SOCS3, Transcriptionally Activated by NR4A1, Induces Apoptosis and Extracellular Matrix Degradation of Vaginal Fibroblasts in Pelvic Organ Prolapse
Background: Pelvic organ prolapse (POP) is a common gynecological chronic disorder. Human vaginal fibroblasts (HVFs) that maintain the integrity of vaginal wall tissues are essential for keeping pelvic organs in place. Apoptosis and the degradation of the extracellular matrix in HVFs contribute to the progression of POP. The cytokine signal transduction inhibitor 3 (SOCS3) exerts significant regulatory effects on cell signal transduction pathways, thereby affecting various pathological processes.
Aims: To explore the role and mechanism of SOCS3 on HVFs in the context of POP.
Study design: In vitro cell lines and human-sample study.
Methods: Anterior vaginal wall tissues were obtained from POP or non-POP patients for the analysis of SOCS3 expression. HVFs were isolated from the vaginal tissues of POP patients, and SOCS3 was either overexpressed or knocked down in HVFs via lentivirus infection. Subsequently, the biological function and mechanism of SOCS3 in HVFs were investigated.
Results: SOCS3 was highly expressed in the vaginal tissues of POP patients compared to non-POP patients. Functionally, the overexpression of SOCS3 suppressed cell viability while promoting cell apoptosis in HVFs. The overexpression of SOCS3 also accelerated extracellular matrix degradation (decreasing collagen I, collagen III, and elastin, and increasing MMP2 and MMP9). In terms of mechanism, NR4A1 transcriptionally activated SOCS3 by binding to its promoter. Furthermore, rescue experiments revealed that SOCS3 knockdown hindered NR4A1 overexpression-induced cell apoptosis and extracellular matrix degradation in HVFs.
Conclusion: SOCS3 mediated the apoptotic and extracellular matrix degradation effects of NR4A1 on HVFs, underlining that the restraining of the SOCS3 expression may be a promising strategy for POP treatment.
期刊介绍:
The Balkan Medical Journal (Balkan Med J) is a peer-reviewed open-access international journal that publishes interesting clinical and experimental research conducted in all fields of medicine, interesting case reports and clinical images, invited reviews, editorials, letters, comments and letters to the Editor including reports on publication and research ethics. The journal is the official scientific publication of the Trakya University Faculty of Medicine, Edirne, Turkey and is printed six times a year, in January, March, May, July, September and November. The language of the journal is English.
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