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<p>The pathogenesis of pelvic organ prolapse (POP) is associated with the decline in estrogen levels post-menopause, which ultimately weakens the mechanical properties of pelvic floor connective tissue. Regenerating (REG) family of proteins, particularly REG1B, regulates tissue repair and regeneration through the modulation of cell proliferation and extracellular matrix (ECM) remodeling. In this study, we utilized ovariectomized (OVX) mice, a recognized animal model for human menopause, to elucidate the mechanisms by which REG1B regulates the function of vaginal wall fibroblasts in POP. Expressions of REG1B and fibroblast-to-myofibroblast transition (FMT) markers in vaginal wall tissues from patients with POP and OVX mice were analyzed using immunohistochemistry and Western blot techniques. The effects of REG1B on the proliferation, migration, and invasion of mouse vaginal wall fibroblasts were evaluated using the Cell Counting Kit-8, cell scratch, and transwell invasion assays. REG1B’s impact on fibroblast collagen and ECM metabolism was examined via Western blot. Dual-luciferase reporter and chromatin immunoprecipitation assays validated the transcriptional regulation of REG1B mediated by estrogen receptor beta (ERβ) through direct binding to its promoter region. REG1B was downregulated in the vaginal wall tissues of patients with POP and OVX mice, whereas markers of FMT were upregulated. The knockdown of REG1B suppressed fibroblast proliferation, migration, and invasion, while simultaneously increasing the expression of FMT markers and promoting ECM remodeling. Activation of ERβ enhanced fibroblast proliferation, migration, and invasion by upregulating the expression of REG1B.This study elucidates the mechanism by which ERβ activation promotes fibroblast proliferation, migration, and invasion through REG1B, providing new insights for regenerative medicine approaches in pelvic floor reconstruction. These findings provide a theoretical foundation for understanding the mechanisms of POP and for developing REG1B-targeted preventive and therapeutic strategies.</p>

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Estrogen receptor beta activates regenerating family member 1 beta to modulate fibroblast function in pelvic organ prolapse

  • 期刊论文

  • 发表日期：

    2026年1月10日

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  • Lai Wei,
  • Ying Zhao,
  • Jing Zhu,
  • Zhijun Xia

摘要

The pathogenesis of pelvic organ prolapse (POP) is associated with the decline in estrogen levels post-menopause, which ultimately weakens the mechanical properties of pelvic floor connective tissue. Regenerating (REG) family of proteins, particularly REG1B, regulates tissue repair and regeneration through the modulation of cell proliferation and extracellular matrix (ECM) remodeling. In this study, we utilized ovariectomized (OVX) mice, a recognized animal model for human menopause, to elucidate the mechanisms by which REG1B regulates the function of vaginal wall fibroblasts in POP. Expressions of REG1B and fibroblast-to-myofibroblast transition (FMT) markers in vaginal wall tissues from patients with POP and OVX mice were analyzed using immunohistochemistry and Western blot techniques. The effects of REG1B on the proliferation, migration, and invasion of mouse vaginal wall fibroblasts were evaluated using the Cell Counting Kit-8, cell scratch, and transwell invasion assays. REG1B’s impact on fibroblast collagen and ECM metabolism was examined via Western blot. Dual-luciferase reporter and chromatin immunoprecipitation assays validated the transcriptional regulation of REG1B mediated by estrogen receptor beta (ERβ) through direct binding to its promoter region. REG1B was downregulated in the vaginal wall tissues of patients with POP and OVX mice, whereas markers of FMT were upregulated. The knockdown of REG1B suppressed fibroblast proliferation, migration, and invasion, while simultaneously increasing the expression of FMT markers and promoting ECM remodeling. Activation of ERβ enhanced fibroblast proliferation, migration, and invasion by upregulating the expression of REG1B.This study elucidates the mechanism by which ERβ activation promotes fibroblast proliferation, migration, and invasion through REG1B, providing new insights for regenerative medicine approaches in pelvic floor reconstruction. These findings provide a theoretical foundation for understanding the mechanisms of POP and for developing REG1B-targeted preventive and therapeutic strategies.