title: N-cadherin is depleted from proximal tubules in experimental and human acute kidney injury.
abstract: Ischemia remains the most common cause of acute kidney injury (AKI). Decreased intercellular adhesion and alterations in adhesion molecules may contribute to the loss of renal function observed in AKI. In the present study, we evaluated the distribution of adhesion molecules in the human kidney and analyzed their expression in human and experimental AKI. Specimens of human kidneys obtained from patients with and without AKI were stained for the cell adhesion molecules E-cadherin, N-cadherin and beta-catenin. Experimental AKI in rats was induced by renal artery clamping. Immunostaining and immunoblotting were carried out for E-cadherin, N-cadherin and beta-catenin. Proximal tubule cells from opossum kidneys (OKs) were used to analyze the effect of chemical hypoxia (ATP depletion) in vitro. In the adult human kidney, N-cadherin was expressed in proximal tubules, while E-cadherin was expressed in other nephron segments. beta-Catenin was expressed in both proximal and distal tubules. In human AKI and in ischemic rat kidneys, N-cadherin immunostaining was depleted from proximal tubules. There was no change in E-cadherin or beta-catenin. In vitro, OK cells expressed N-cadherin only in the presence of collagen, and ATP depletion led to a depletion of N-cadherin. Collagen IV staining was reduced in ischemic rat kidneys compared to controls. The results of the study suggest that N-cadherin may play a significant role in human and experimental AKI.
authors.affiliation: Department of Nephrology, University Hospital Essen, University Duisburg-Essen, Essen, Germany. jens.nuernberger@uni-due.de
authors.forename: Jens
authors.initials: J
authors.lastname: Nürnberger
authors.forename: Thorsten
authors.initials: T
authors.lastname: Feldkamp
authors.forename: Rosmaria
authors.initials: R
authors.lastname: Kavapurackal
authors.forename: Anabelle
authors.initials: A
authors.lastname: Opazo Saez
authors.forename: Jan
authors.initials: J
authors.lastname: Becker
authors.forename: Markus
authors.initials: M
authors.lastname: Hörbelt
authors.forename: Andreas
authors.initials: A
authors.lastname: Kribben
mesh_terms: D058186:Acute Kidney Injury / Q000503:physiopathology*; D000818:Animals; D015820:Cadherins / Q000737:chemistry* / Q000145:classification / Q000378:metabolism*; D002478:Cells, Cultured; D004195:Disease Models, Animal; D006801:Humans; D007150:Immunohistochemistry; D007668:Kidney / Q000293:injuries* / Q000378:metabolism* / Q000473:pathology; D007687:Kidney Tubules, Proximal / Q000378:metabolism*; D008297:Male; D009893:Opossums; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D015820:Cadherins