TGF-β1 induces epithelial-mesenchymal transition and fibrosis of ureteral epithelial cells via targeting RACK1 in ureteropelvic junction obstruction

Background Ureteropelvic junction obstruction (UPJO) is a frequent cause of congenital hydronephrosis. It involves both structural and functional changes at the ureteropelvic junction (UPJ), where the ureter connects with the renal pelvis. The mechanisms behind tissue remodeling and fibrosis in this condition are not fully understood. This study explores the role of epithelial-mesenchymal transition (EMT) and examines how receptor for activated C kinase 1 (RACK1) may regulate this process in UPJO. Methods Stenotic UPJ tissues were collected from patients with congenital UPJO and analyzed for EMT and RACK1 expression. An in vitro model was established using SV-HUC-1 ureteral epithelial cells treated with TGF-β1 to induce EMT. RACK1 expression was manipulated by siRNA, and changes in EMT-related markers, Smad2/3 and p65 signaling, extracellular matrix proteins, cell proliferation, and migration were evaluated by qRT-PCR, western blotting, and functional assays, respectively. Results EMT features, including increased expression of N-cadherin, β-catenin, Vimentin, and ECM-related proteins (COL1A1, FN1, α-SMA), and decreased E-cadherin expression, were observed in both UPJO tissues and TGF-β1–treated cells. RACK1 was significantly upregulated in stenotic tissues and after TGF-β1 stimulation. RACK1 knockdown suppressed Smad2/3 and p65 activation, inhibited EMT progression, and reduced cell proliferation and migration. Conclusion EMT contributes to tissue remodeling and fibrosis in congenital UPJO. RACK1 promotes TGF-β1–induced EMT through activation of Smad2/3 and p65 signaling. These findings provide new insights into the pathogenesis of UPJO and suggest RACK1 as a potential target for therapeutic intervention.