{"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}
引用次数: 0
Abstract
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.
The journal is based on independent and unbiased double-blinded peer-reviewed principles. Only unpublished papers that are not under review for publication elsewhere can be submitted. Balkan Medical Journal does not accept multiple submission and duplicate submission even though the previous one was published in a different language. The authors are responsible for the scientific content of the material to be published. The Balkan Medical Journal reserves the right to request any research materials on which the paper is based.
The Balkan Medical Journal encourages and enables academicians, researchers, specialists and primary care physicians of Balkan countries to publish their valuable research in all branches of medicine. The primary aim of the journal is to publish original articles with high scientific and ethical quality and serve as a good example of medical publications in the Balkans as well as in the World.