Journal
INTERNATIONAL UROGYNECOLOGY JOURNAL
Volume 33, Issue 8, Pages 2203-2212Publisher
SPRINGER LONDON LTD
DOI: 10.1007/s00192-021-04850-7
Keywords
Pelvic organ prolapse; Human uterosacral ligament fibroblasts; Mechanical stress; p38 MAPK pathway
Categories
Funding
- National Natural Science Foundation of China (NSFC) [81671442, 81971366]
- Beijing Natural Science Foundation [Z190021]
- CAMS Innovation Fund for Medical Sciences [CIMFS-2020-I2M-CT-B-043]
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The study found that hUSLFs from POP patients were larger and longer with rearrangement of F-actin. Collagen I and III expression were downregulated, MMP1 expression was upregulated, and apoptosis rate increased in POP patients. Mechanical stress induced cell morphological changes, ECM remodeling, and apoptosis, with potential involvement of the p38 MAPK pathway.
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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