TY - MGZN T1 - Tubulointerstitial De Novo Expression of the ?8 Integrin Chain in a Rodent Model of Renal Fibrosis ? A Potential Target for Anti-Fibrotic Therapy? T3 - PLoS ONE 7.11 (2012): 15.11.2012 A1 - Hartner,Andrea A1 - Menendez-Castro,Carlos A1 - Cordasic,Nada A1 - Marek,Ines A1 - Volkert,Gudrun A1 - Klanke,Bernd A1 - Rascher,Wolfgang A1 - Hilgers,Karl F. Y1 - 2012/11/16 N2 - In the normal kidney, the ?8 integrin chain is expressed only on mesangial cells and vascular smooth muscle cells. ?8 integrin ligates several matrix molecules including fibronectin, osteopontin and fibrillin-1. Recently, we detected de novo expression of ?8 integrin on epithelial cells in renal cysts. We hypothesized that the ?8 integrin chain is induced in tubular epithelia undergoing dedifferentiation and contributes to the fibrotic response in the tubulointerstitium (TI) after unilateral ureteral obstruction (UUO). After induction of UUO in rats by ligation of the right ureter, increased expression of the ?8 integrin chain and its ligands was observed. In the TI, ?8 integrin was localized to cytokeratin-positive epithelial cells and to interstitial fibroblasts; and colocalized with its ligands. In mice underexpressing ?8 integrin UUO led to collagen deposition and fibroblast activation comparable to wild types. Mice lacking ?8 integrin showed even more TI damage, fibroblast activation and collagen deposition after UUO compared to wild type mice. We conclude that the expression of the ?8 integrin chain and its ligands is strongly induced in the TI after UUO, but underexpression of ?8 integrin does not attenuate TI fibrosis. Mice lacking the ?8 integrin chain are even more susceptible to TI damage than wild type mice. Thus, interactions of ?8 integrin with its ligands do not seem to contribute to the development or progression of TI fibrosis in UUO. Targeting ?8 integrin might not be a useful approach for anti-fibrotic therapy. KW - - CY - Erlangen PB - Universitätsbibliothek der Universität Erlangen-Nürnberg AD - Universitätsstraße. 4, 91054 Erlangen L2 - http://www.opus.ub.uni-erlangen.de/opus/volltexte/2012/3886 ER -