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3
1-integrin in renal ischemic
injury and repair in vivo
1 Department of Surgery, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02215; and 2 Department of Surgery, University of Cincinnati College of Medicine, Cincinnati, Ohio 45219-0581
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 rat kidney after 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 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 ~220 kDa, possibly corresponding to a precursor of one of the three
laminin-5 chains. Immunoblotting and immunostaining also demonstrate
significantly increased expression and altered localization of the
3-integrin subunit, a receptor for laminin-5. These
results indicate that there is induction of a laminin isoform, possibly laminin-5, and
3
1-integrin 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.
extracellular matrix; epithelial regeneration; acute renal failure
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