Abstract
Pelvic organ prolapse (POP) is a common disorder among women that negatively affects women’s quality of life. Early growth response 2 (EGR2) is a transcription factor that regulates cell growth. The present study aimed to explore the role of EGR2 in POP progression and provided a new target for the treatment and prevention of POP. Firstly, we extracted primary vaginal anterior wall fibroblasts from POP tissues and non-POP tissues and then constructed an EGR2-silencing lentivirus for further study. Immunoblotting, qPCR, TUNEL assay, CCK-8 assay, dual luciferase assay, and ELISA assay were carried out. EGR2 expression was much higher in POP tissues than in control tissues, and EGR2 expression positively correlated with cytokine signaling 3 (SOCS3) expression. Knockdown of EGR2 increased cell proliferation, upregulated PCNA expression, and reduced apoptosis in POP fibroblasts. Moreover, we found that the knockdown of EGR2 increased COL1A1, COL3A1, and Elastin expression and decreased MMP2 and MMP9 activities, and knockdown of EGR2 increased TGF-β/Smad pathway activity in POP fibroblasts. Interestingly, the results of dual luciferase assay demonstrated that EGR2 was able to increase SOCS3 transcriptional activity. EGR2 knockdown alleviated the apoptosis of POP fibroblasts by reducing SOCS3 expression and improving the proliferation and collagen synthesis of POP fibroblasts. Overall, our study illustrated that EGR2 was highly expressed in POP tissues, and knockdown of EGR2 alleviated apoptosis and reduced matrix degradation in POP fibroblasts. This study might provide a new insight into the pathogenesis of POP.
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Data availability
The datasets analyzed during the current study are available from the corresponding author on reasonable request.
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This work was supported by the National Natural Science Foundation of China (no. 82271613); the National Key R&D Program of China (no. 2021YFC2701302); the Basic Scientific Research Project of Colleges and Universities of Liaoning Province (no. LJKMZ20221168).
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X.J.: writing—original draft, writing—review and editing, methodology, software, validation, formal analysis, and investigation. H.X.: writing—original draft, methodology, software, investigation, visualization, and data curation. Q.H.: methodology, validation, formal analysis, and visualization. Y.Y.: software, data curation, and visualization. M.Q.: formal analysis and visualization. Z.X.: conceptualization, writing—review and editing, and supervision.
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The written informed consent was obtained from all participants before specimen collection. This study was approved by the Shengjing Hospital of China Medical University Ethics Committee (2022PS040K) and complied with the principles of the Declaration of Helsinki.
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Jin, X., Xu, H., Hu, Q. et al. Early growth response 2, a novel target of pelvic organ prolapse, is highly expressed in anterior vaginal wall tissues with pelvic organ prolapse. Histochem Cell Biol 161, 195–205 (2024). https://doi.org/10.1007/s00418-023-02240-2
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DOI: https://doi.org/10.1007/s00418-023-02240-2