Molecular mechanisms of pelvic organ prolapse influenced by FBLN5 via FOSL1/miR-222/MEIS1/COL3A1 axis.

This study delves into the role of FBLN5 in pelvic organ prolapse (POP) and its molecular mechanisms, focusing on the FOSL1/miR-222/MEIS1/COL3A1 axis. Gene relationships linked to POP were confirmed using bioinformatics databases like GEO and StarBase. Primary human uterosacral ligament fibroblasts (hUSLF) were extracted and subjected to mechanical stretching. Cellular cytoskeletal changes were examined via phalloidin staining, intracellular ROS levels with a ROS kit, cell apoptosis through flow cytometry, and cell senescence using β-galactosidase staining. FBLN5's downstream targets were identified, and the interaction between FOSL1 and miR-222 and miR-222 and MEIS1 were validated using assays. In rat models, the role of FBLN5 in POP was assessed using bladder pressure tests. Results indicated diminished FBLN5 expression in uterine prolapse. Enhanced FBLN5 countered mechanical damage in hUSLF cells by downregulating FOSL1. FOSL1 augmented miR-222, inhibiting MEIS1, which subsequently fostered COL3A1 transcription. In rat models, the absence of FBLN5 exacerbated POP by influencing the FOSL1/miR-222/MEIS1/COL3A1 pathway. FBLN5's protective role likely involves regulating the above axis and boosting COL3A1 expression. Further research is needed to validate the effectiveness and safety of this mechanism in human patients and to propose potential new treatment options. • FBLN5 alleviates pelvic organ prolapse by regulating the FOSL1/miR-222/MEIS1/COL3A1 axis. • Bioinformatics analysis reveals that FBLN5 is significantly underexpressed in uterine organ prolapse. • Overexpression of FBLN5 can inhibit cell damage caused by mechanical traction. • FOSL1 promotes the expression of miR-222 through transcription. • MEIS1 can alleviate cell damage caused by mechanical traction by promoting the transcription of COL3A1. [ABSTRACT FROM AUTHOR]