miR-200b-3p enriched exosomes promote smooth muscle cell proliferation and fibrosis via targeting ZO-1 in bladder outlet obstruction

Bladder outlet obstruction (BOO) induces urinary bladder wall remodeling. However, the function of exosomal miRNAs from bladder smooth muscle cells (BSMCs) in BOO development remains unclear. Differentially expressed miRNA profiles in BSMC-derived exosomes from BOO rat models and normal rats were analyzed using miRNA sequencing. LPS-induced BSMCs were treated with exosomes from BOO-extracted BSMCs. The uptake of exosomes in BSMCs was assessed by PKH26 fuorescent dye. The protein levels of MCP-1, IL-1β, TNF-α, α-SMA, and collagen I were detected by western blotting and qPCR analysis. Cell proliferation and apoptosis were assessed by CCK-8, EdU, and flow cytometry, respectively. The interaction between miR-200b-3p and zonula occludens-1 (ZO-1) 3'UTR was analyzed by luciferase reporter gene assay. Results indicated that miRNA-200b-3p was upregulated in BSMC-derived exosomes from BOO rats compared with the sham group. Treatment with exosomes from BOO-extracted BSMCs further aggravated LPS-induced BSMC proliferation, inflammation, and fibrosis. Inhibition of miR-200b-3p attenuated these effects, which were restored by silencing ZO-1 expression in BSMCs. We identified upregulation of exosomal miR-200b-3p from BSMCs in BOO rats and demonstrated that BSMC-derived exosomes enhanced proliferation, inflammation, and fibrosis of BSMCs via miR-200b-3p/ZO-1 axis. Our work identifies a potential target for diagnosis and therapy in BOO.