TGF-beta Mediated Epithelial-Mesenchymal Transition in Autosomal Dominant Polycystic Kidney Disease.
10.3349/ymj.2009.50.1.105
- Author:
Seung Wan CHEA
1
;
Kyu Beck LEE
Author Information
1. Department of Pathology, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea.
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
Epithelial mesenchymal transition;
antosomal dominant polycystic kidney disease
- MeSH:
Aged;
Biological Markers/metabolism;
Cell Division;
Disease Progression;
Epithelial Cells/*pathology;
Female;
Fibrosis;
Humans;
Kidney Glomerulus/pathology;
Kidney Tubules/pathology;
Male;
Mesoderm/*pathology;
Middle Aged;
Polycystic Kidney, Autosomal Dominant/*metabolism/*pathology;
Transforming Growth Factor beta/*metabolism
- From:Yonsei Medical Journal
2009;50(1):105-111
- CountryRepublic of Korea
- Language:English
-
Abstract:
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 alpha-SMA, E-cadherin, vimentin, TGF-beta1 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 alpha-SMA+ myofibroblasts in ADPKD. Cystic tubular epithelial cells in ADPKD lost epithelial marker (E-cadherin) and expressed mesenchymal markers (alpha-SMA, vimentin). There were significant increases of alpha-SMA (34.3 +/- 11.7% vs 0.9 +/- 1.5%), vimentin (19.9 +/- 3.9% vs 3.3 +/- 1.4%), TGF-beta1 (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-beta, Smad 2/3 and markers of EMT. It suggests that TGF-beta mediated EMT has a role in progression of ADPKD.
