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 transforming growth factor-beta 1 (TGF-β1) to induce EMT. RACK1 expression was manipulated by small interfering RNA (siRNA), and changes in EMT-related markers, Smad2/3 and p65 signaling, extracellular matrix (ECM) proteins, cell proliferation, and migration were evaluated by real-time quantitative polymerase chain reaction (RT-qPCR), 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 features, and reduced cell proliferation and migration.

CONCLUSIONS

EMT features are associated with 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.