ISSN : 2146-3123
E-ISSN : 2146-3131

SOCS3, Transcriptionally Activated by NR4A1, Induces Apoptosis and Extracellular Matrix Degradation of Vaginal Fibroblasts in Pelvic Organ Prolapse
Xin Jin1, Qing Hu1, Meiying Qin1, Yitong Yin1, Zhijun Xia1
1Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, China
DOI : 10.4274/balkanmedj.galenos.2023.2023-10-60

Background: Pelvic organ prolapse (POP) is a common gynecologicalchronic disorder. Human vaginal fibroblasts (HVFs) that maintain theintegrity of vaginal wall tissues are essential for keeping pelvic organsin place. Apoptosis and the degradation of the extracellular matrix(ECM) in HVFs contribute to the progression of POP. The cytokinesignal transduction inhibitor 3 (SOCS3) exerts significant regulatoryeffects on cell signal transduction pathways, thereby affecting variouspathological processes.
Aims: To explore the role and mechanism of SOCS3 on HVFs in thecontext of POP.
Study Design: Experimental study.
Methods: Anterior vaginal wall tissues were obtained from POPor non-POP patients for the analysis of SOCS3 expression. HVFswere isolated from the vaginal tissues of POP patients, and SOCS3was either overexpressed or knocked down in HVFs via lentivirusinfection. Subsequently, the biological function and mechanism ofSOCS3 in HVFs were investigated.
Results: SOCS3 was highly expressed in the vaginal tissues ofPOP patients compared to non-POP patients. Functionally, theoverexpression of SOCS3 suppressed cell viability while promotingcell apoptosis in HVFs. The overexpression of SOCS3 also acceleratedECM degradation (decreasing collagen I, collagen III, and elastin,and increasing MMP2 and MMP9). In terms of mechanism, NR4A1transcriptionally activated SOCS3 by binding to its promoter.Furthermore, rescue experiments revealed that SOCS3 knockdownhindered NR4A1 overexpression-induced cell apoptosis and ECMdegradation in HVFs.
Conclusion: SOCS3 mediated the apoptotic and ECM degradationeffects of NR4A1 on HVFs, underlining that the restraining of theSOCS3 expression may be a promising strategy for POP treatment.

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