TGF-β mediated epithelial-mesenchymal transition in autosomal dominant polycystic kidney disease

Purpose: Recent studies have showed that epithelial-mesenchymal transition (EMT) is a key process of glomerular and tubulointerstitial pathology in many chronic kidney diseases. However, there are no data of EMT in humane autosomal dominant polycystic kidney disease (ADPKD). Patients and Methods: ADPKD kidneys (N = 5) with end stage renal disease (ESRD) and control kidneys (N = 4) were analyzed immnunohistochemically. We evaluated α-SMA, E-cadherin, vimentin, TGF-β1 and Smad 2/3 expression in ADPKD and compared them with those in control kidney. These immunohistochemical findings were quantitatively analyzed by computer-assisted image analyzer and positive tubules (%). Results: There were severe interstitial fibrosis and proliferation of α-SMA+ myofibroblasts in ADPKD. Cystic tubular epithelial cells in ADPKD lost epithelial marker (E-cadherin) and expressed mesenchymal markers (α-SMA, vimentin). There were significant increases of α-SMA (34.3 ± 11.7% vs 0.9 ± 1.5%), vimentin (19.9 ± 3.9% vs 3.3 ± 1.4%), TGF-β1 (5.42 ± 2.83% vs 0%) and Smad 2/3 (3.4 ± 1.7% vs 0.7 ± 0.6%) in ADPKD kidneys compared with control kidneys evidenced by computer-assisted image analyzer. When we analyze the positive tubules (%), the results were the same as computer-assisted image analyzer. Conclusion: Our results showed that the end stage of ADPKD is associated with TGF-β, Smad 2/3 and markers of EMT. It suggests that TGF-β mediated EMT has a role in progression of ADPKD.