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Am J Physiol Renal Physiol (July 16, 2002). doi:10.1152/ajprenal.00176.2002
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Articles in PresS, published online ahead of print July 16, 2002
Am J Physiol Renal Physiol, 10.1152/ajprenal.00176.2002
Submitted on May 3, 2002
Accepted on July 9, 2002

Induction of a Laminin Isoform and the {alpha}3ß1 Integrin in Renal Ischemic Injury and Repair In Vivo

Anna Zuk1 and Karl S. Matlin2*

1 Department of Surgery, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA
2 Department of Surgery, University of Cincinnati College of Medicine, Cincinnati, OH, USA

* To whom correspondence should be addressed. E-mail: karl.matlin{at}uc.edu.

Ischemic injury to the kidney, a major cause of acute renal failure, leads to the detachment and loss of numerous tubular epithelial cells. Integrin-laminin interactions may promote regeneration of the damaged epithelium by influencing kidney epithelial cell adhesion and differentiation. Laminins are major structural components of basement membranes. Of the various laminin isoforms, laminin-5 is of particular interest because of its proposed role in the healing of skin wounds. In this study, we investigate the expression of laminin-5 in the rat kidney following unilateral ischemia. Using a polyclonal antibody generated against laminin-5, we find that immunostaining is confined to the basement membranes of collecting ducts in the papilla and the major and minor calyces in the normal kidney. With injury and regeneration, however, immunostaining becomes much more intense and widespread in basement membranes along the nephron. Immunoblotting of ischemic kidney extracts reveals significantly increased expression of a polypeptide of approximately 220kD, possibly corresponding to a precursor of one of the three laminin-5 chains. Immunoblotting and immunostaining also demonstrates significantly increased expression and altered localization of the {alpha}3 integrin subunit, a receptor for laminin-5. These results indicate that there is induction of a laminin isoform, possibly laminin-5, and the integrin {alpha}3ß1 in the ischemic kidney, and may implicate this receptor-ligand combination in the pathogenesis of acute renal failure and/or repair of the injured kidney epithelium.




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