The molecular mechanism of serum exosome miR-133b regulating the proliferation and apoptosis of vaginal smooth muscle cells by targeting AXUD1 to regulate Wnt / β-catenin signaling pathway

Pelvic organ prolapse (POP) is a prevalent disorder associated with dysfunctional pelvic support tissues. Recent studies have underscored the role of exosomes, which transport regulatory molecules such as miRNAs, in the progression of this disease. In this study, we extracted and characterized serum exosomes, cultured primary vaginal smooth muscle cells, and conducted functional assays. Notably, miR-133b was identified as being significantly downregulated in serum exosomes from POP patients, alongside disrupted smooth muscle organization, reduced α-SMA levels, elevated AXUD1 expression, and increased apoptosis. Exosomal miR-133b was found to promote cell proliferation and inhibit apoptosis; conversely, its target gene AXUD1, which is highly expressed in POP, counteracted these protective effects. Further analysis indicated that miR-133b modulates both the Bcl-2/Bax-Caspase-3 apoptotic pathway and the Wnt/β-catenin signaling axis through the inhibition of AXUD1, thereby influencing cellular homeostasis. In conclusion, the structural impairment of the anterior vaginal wall, the upregulation of AXUD1, and the decreased expression of miR-133b, Wnt16, and β-catenin are closely associated with the development of POP. Serum exosome-derived miR-133b may regulate smooth muscle cell proliferation and apoptosis via the AXUD1/Wnt/β-catenin pathway, thereby contributing to the pathogenesis of POP.