1. Mechanical stress influences the morphology and function of human uterosacral ligament fibroblasts and activates the p38 MAPK pathway
- Author
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Lan Zhu, Ya-Pei Zhu, Tao Guo, Ting Xie, Zhijing Sun, and Lei Li
- Subjects
genetic structures ,MMP1 ,Urology ,p38 mitogen-activated protein kinases ,Uterosacral ligament ,Matrix metalloproteinase ,p38 Mitogen-Activated Protein Kinases ,Collagen Type I ,Pelvic Organ Prolapse ,Extracellular matrix ,03 medical and health sciences ,0302 clinical medicine ,Downregulation and upregulation ,Humans ,Medicine ,Cytoskeleton ,Aged ,030304 developmental biology ,0303 health sciences ,Ligaments ,030219 obstetrics & reproductive medicine ,business.industry ,Obstetrics and Gynecology ,Fibroblasts ,Cell biology ,medicine.anatomical_structure ,Apoptosis ,Quality of Life ,Female ,Stress, Mechanical ,Matrix Metalloproteinase 1 ,business - 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.
- Published
- 2021
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