Role of the integrin‑&beta;1/TGF‑&beta;1 signaling pathway in the pathogenesis of pelvic organ prolapse: A study on vaginal wall tissue alterations and molecular dysfunction

Kong,Min; Wang,Zhuo; Hao,Yao; Shi,Yueyue; Yang,Xin; Djurist,Ngenzi Richard; Li,Yan

doi:10.3892/mmr.2025.13469

Role of the integrin‑β1/TGF‑β1 signaling pathway in the pathogenesis of pelvic organ prolapse: A study on vaginal wall tissue alterations and molecular dysfunction

Authors:
- Min Kong
- Zhuo Wang
- Yao Hao
- Yueyue Shi
- Xin Yang
- Ngenzi Richard Djurist
- Yan Li
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Affiliations: Department of Gynecology, General Hospital of Ningxia Medical University, Yinchuan, Ningxia Hui Autonomous Region 750004, P.R. China, School of Basic Medical Sciences, Ningxia Medical University, Yinchuan, Ningxia Hui Autonomous Region 750004, P.R. China
Published online on: February 20, 2025 https://doi.org/10.3892/mmr.2025.13469
Article Number: 104
Copyright: © Kong et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Pelvic organ prolapse (POP) is a prevalent condition among middle‑aged and older women, and is associated with the irregular production and breakdown of the extracellular matrix. Mechanical forces serve a key role in preserving the equilibrium between matrix synthesis and degradation, thereby supporting the structural integrity of pelvic floor tissues. The aim of the present study was to investigate alterations in the composition of vaginal wall tissues in individuals suffering from POP and to investigate the molecular mechanisms through which mechanical forces trigger fibroblast apoptosis and influence collagen expression via the integrin‑β1/TGF‑β1 signaling pathway. Masson's trichrome and Elastica van Gieson staining were used to examine the pathological alterations in the tissue associated with POP. Analysis of immunofluorescence, western blotting and reverse transcription‑quantitative PCR data was performed to assess changes in the levels of proteins and genes such as collagen, integrin‑β1, TGF‑β1, MMP‑1 and tissue inhibitor of metalloproteinase‑1 (TIMP‑1). Fibroblasts were incubated with an integrin‑β1 antagonist RGD peptide to mimic cellular injury induced by mechanical forces, and cell migration and apoptosis were analyzed using scratch assays and flow cytometry. Cytoskeletal alterations were detected via immunofluorescence staining, and western blot analysis was conducted to examine the expression levels of integrin‑β1, TGF‑β1, TIMP‑1, MMP‑1, collagen type I α1 chain (COL1A1) and collagen type III α1 chain (COL3A1) across various groups. Analysis revealed that in the POP group, the collagen fibers in the vaginal wall tissues were loose and irregularly arranged, the number of elastic fibers was reduced and the structure was degraded. Furthermore, stress fibers were incomplete and their functions were impaired, resulting in damage to the connective tissue structure of the pelvic floor. Integrin‑β1 was key for fibroblast migration, apoptosis and collagen synthesis. Additionally, the integrin‑β1/TGF‑β1 signaling pathway served a role in mediating fibroblast apoptosis, and influencing the synthesis and metabolism of COL1A1 and COL3A1 induced by mechanical forces. Understanding the underlying pathogenesis of pelvic floor organ prolapse could pave the way for future investigations into innovative prevention and treatment strategies.

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