Mechanical stretching induces fibroblasts apoptosis through activating Piezo1 and then destroying actin cytoskeleton

Abstract

Abstract Ligaments and muscles maintain the anatomical positions of pelvic floor organs. Stress urinary incontinence (SUI) occurs when pelvic floor tissues are repeatedly stimulated with excessive mechanical tension that is beyond the capacity of ligaments or muscles to endure. In addition, cells respond mechanically to mechanical stimulation by reconstituting the Piezo1 and cytoskeletal system. This study sought to determine how Piezo1 and actin cytoskeletal contribute to MS-induced apoptosis in human anterior vaginal wall fibroblasts (hAVWFs) and the mechanisms involved. A four-point bending device was used to provide mechanical stretching to establish a cellular mechanical damage model . MS significantly induced apoptosis of hAVWFs from non-SUI patients, which exhibited apoptosis rates comparable to those of SUI patients, and silencing of Piezo1 decreased the MS-induced apoptosis. However, the disassembly of actin cytoskeleton suppressed the protective effect of Piezo1 silencing from MS. Based on these findings, Piezo1 links the actin cytoskeleton to apoptosis in hAVWFs, providing insight into the clinical diagnosis and treatment of SUI.