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International Urogynecology Journal

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Open Access 25-05-2021 | Original Article

Mechanical stress influences the morphology and function of human uterosacral ligament fibroblasts and activates the p38 MAPK pathway

Authors: Yapei Zhu, Lei Li, Ting Xie, Tao Guo, Lan Zhu, Zhijing Sun

Published in: International Urogynecology Journal | Issue 8/2022

Abstract

Introduction and hypothesis

Pelvic organ prolapse (POP) is a common condition in older women that affects quality of life. Mechanical injury of the pelvic floor support system contributes to POP development. In our study, we aimed to examine the mechanical damage to human uterosacral ligament fibroblasts (hUSLFs) to preliminarily explore the mechanism of mechanical transduction in POP.

Methods

hUSLFs were derived from POP and non-POP patients. Mechanical stress was induced by the FX-5000 T-cell stress loading system. Student’s t-test was used for comparisons between different groups.

Results

We found that hUSLFs from POP patients were larger and longer than those from non-POP patients and exhibited cytoskeleton F-actin rearrangement. Collagen I and III expression levels were lower and matrix metalloproteinase 1 (MMP1) levels were higher in POP patients than in non-POP patients. Additionally, the apoptosis rate was significantly increased in POP patients compared to non-POP patients. After mechanical stretching, hUSLFs underwent a POP-like transformation. Cells became longer, and the cytoskeleton became thicker and rearranged. The extracellular matrix (ECM) was remodelled because of the upregulation of collagen I and III expression and downregulation of MMP1 expression. Mechanical stress also induced hUSLF apoptosis. Notably, we found that the p38 MAPK pathway was activated by mechanical stretching.

Conclusions

Mechanical stress induced morphological changes in ligament fibroblasts, leading to cytoskeleton and ECM remodelling and cell apoptosis. p38 MAPK might be involved in this process, providing novel insights into the mechanical biology of and possible therapies for this disease.

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Title: Mechanical stress influences the morphology and function of human uterosacral ligament fibroblasts and activates the p38 MAPK pathway
Authors: Yapei Zhu
Lei Li
Ting Xie
Tao Guo
Lan Zhu
Zhijing Sun
Publication date: 25-05-2021
Publisher: Springer International Publishing
Published in: International Urogynecology Journal / Issue 8/2022
Print ISSN: 0937-3462
Electronic ISSN: 1433-3023
DOI: https://doi.org/10.1007/s00192-021-04850-7

At a glance: The STEP trials

Springer Medicine

Mechanical stress influences the morphology and function of human uterosacral ligament fibroblasts and activates the p38 MAPK pathway

Abstract

Introduction and hypothesis

Methods

Results

Conclusions

At a glance: The STEP trials

Springer Medicine

Abstract

Introduction and hypothesis

Methods

Results

Conclusions

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