TGF-β1 mediates epithelial-mesenchymal transition in interstitial cystitis through the regulation of ROCK.

Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic condition characterised by bladder pain, urinary frequency, and urgency, which impacts quality of life. The pathogenesis remains unclear, though bladder fibrosis resulting from epithelial-mesenchymal transition (EMT) plays a key role. Transforming growth factor-β1 (TGF-β1) is a critical inducer of EMT and has been implicated in IC/BPS, although the molecular mechanisms are not fully understood. Rho-associated kinase (ROCK), a downstream effector of TGF-β1, may be involved in this process. This study aimed to explore the role of TGF-β1 in regulating EMT through ROCK in IC/BPS. An interstitial cystitis model in rats was established by intraperitoneal injection of cyclophosphamide (CYP). EMT in SV-HUC-1 cells was induced with recombinant TGF-β1 and modulated by treatment with the TGF-β receptor inhibitor SB505124 and the ROCK inhibitor Y-27632. Mechanical pain sensitivity was assessed using the Von Frey test, and serum TGF-β1 levels were measured by ELISA. Fibrosis markers in bladder tissue and cell were analyzed by H&E staining, Masson's trichrome, Western blotting, immunohistochemistry, and immunofluorescence. Results showed CYP-induced rats exhibited mechanical pain, elevated serum TGF-β1, and aggravated bladder fibrosis. In addition, TGF-β1, ROCK, and fibrosis-related proteins (vimentin, N-cadherin, fibroblast-specific protein 1, α-smooth muscle actin) were upregulated, while E-cadherin was reduced. Inhibition of TGF-β1 and ROCK reversed these changes, though the ROCK inhibitor did not affect TGF-β1 levels. This study demonstrates that TGF-β1 mediates EMT in bladder epithelial cells via ROCK, contributing to IC/BPS pathogenesis, and suggests that TGF-β1 and ROCK inhibitors may offer potential therapeutic strategies for IC/BPS.