TGF-beta mediated epithelial-mesenchymal transition in autosomal dominant polycystic kidney disease.
OBJECTIVE
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).


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.


CONCLUSIONS
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.
Chea
Seung Wan
SW
Department of Pathology, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea.
Lee
Kyu-Beck
KB
D000368:Aged; D015415:Biomarkers / Q000378:metabolism; D002455:Cell Division; D018450:Disease Progression; D004847:Epithelial Cells / Q000473:pathology*; D005260:Female; D005355:Fibrosis; D006801:Humans; D007678:Kidney Glomerulus / Q000473:pathology; D007684:Kidney Tubules / Q000473:pathology; D008297:Male; D008648:Mesoderm / Q000473:pathology*; D008875:Middle Aged; D016891:Polycystic Kidney, Autosomal Dominant / Q000378:metabolism* / Q000473:pathology*; D016212:Transforming Growth Factor beta / Q000378:metabolism*
D015415:Biomarkers; D016212:Transforming Growth Factor beta