Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
National Clinical Research Center for Obstetric & Gynecologic Disease, Beijing, China.
Int Urogynecol J. 2022 Aug;33(8):2203-2212. doi: 10.1007/s00192-021-04850-7. Epub 2021 May 25.
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.
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.
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.
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.
盆腔器官脱垂（POP）是老年女性常见的疾病，影响生活质量。盆腔底部支持系统的机械损伤导致 POP 的发展。在我们的研究中，我们旨在研究人子宫骶骨韧带成纤维细胞（hUSLF）的机械损伤，初步探讨 POP 中机械转导的机制。
hUSLF 来源于 POP 和非 POP 患者。使用 FX-5000 T 细胞应激加载系统诱导机械应激。使用 Student's t 检验比较不同组之间的差异。
我们发现，来自 POP 患者的 hUSLF 比非 POP 患者的更大更长，并表现出细胞骨架 F-actin 重排。与非 POP 患者相比，POP 患者的胶原 I 和 III 表达水平较低，基质金属蛋白酶 1（MMP1）水平较高，凋亡率显著增加。机械拉伸后，hUSLF 发生类似于 POP 的转化。细胞变得更长，细胞骨架变厚并重新排列。细胞外基质（ECM）由于胶原 I 和 III 表达上调和 MMP1 表达下调而重塑。机械应激还诱导 hUSLF 凋亡。值得注意的是，我们发现机械拉伸激活了 p38 MAPK 通路。
机械应激诱导韧带成纤维细胞形态变化，导致细胞骨架和 ECM 重塑以及细胞凋亡。p38 MAPK 可能参与这一过程，为该疾病的机械生物学和可能的治疗方法提供了新的见解。
