Background The anatomical positions of pelvic floor organs are maintained mainly by ligaments and muscles. Long-term excessive mechanical tension stimulation of pelvic floor tissue beyond the endurance of ligaments or muscles will lead to the occurrence of pelvic organ prolapse (POP). In addition, cytoskeletal reconstitution is a key process by which cells respond to mechanical stimulation. The aim of the present study was to investigate the protective effect of actin cytoskeleton in resist mechanical stretching (MS)-induced apoptosis of parametrial ligament fibroblasts (PLFs) and the underlying mechanisms.
Methods 8 women who underwent hysterectomy surgery for reasons excluding the presence of malignant tumors and POP served as controls, and 7 patients who underwent hysterectomy surgery for only advanced POP comprised the POP group. MS was provided by a fourpoint bending device. We examined the effects of MS on actin cytoskeleton and apoptosis of PLFs. Then the apoptosis was detected after latrunculin A (Lat-A, a potent inhibitor of actin) exposure and the interference of Nr4a1.
Results MS could significantly induce apoptosis of PLFs from non-POP patients, which exhibited an apoptosis rate close to that of PLFs from POP patients, and the apoptosis rate was higher following latrunculin A treatment. In addition, Nr4a1 and Bax expression was increased while Bcl-2 and caspase-3 expression was clearly decreased after treatment with MS and Lat-A. However, the MS-induced apoptosis of PLFs was reduced when treatment with siRNA targeting Nr4a1 was used to downregulate the level of Nr4a1.
Conclusions These outcomes reveal a novel mechanism that links the actin cytoskeleton and apoptosis in PLFs by Nr4a1; this mechanism will provide insight into the clinical diagnosis and treatment of POP.