Induction of a laminin isoform and alpha(3)beta(1)-integrin in renal ischemic injury and repair in vivo.
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 approximately 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 alpha(3)-integrin subunit, a receptor for laminin-5. These results indicate that there is induction of a laminin isoform, possibly laminin-5, and alpha(3)beta(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.
Zuk
Anna
A
Department of Surgery, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02215, USA.
Matlin
Karl S
KS
D058186:Acute Kidney Injury / Q000378:metabolism*; D000818:Animals; D000918:Antibody Specificity; D015815:Cell Adhesion Molecules / Q000032:analysis / Q000096:biosynthesis* / Q000276:immunology; D005109:Extracellular Matrix / Q000378:metabolism; D007150:Immunohistochemistry; D039201:Integrin alpha3beta1 / Q000032:analysis / Q000096:biosynthesis* / Q000276:immunology; D007511:Ischemia / Q000378:metabolism*; D007668:Kidney / Q000737:chemistry / Q000502:physiology*; D051381:Rats; D015854:Up-Regulation / Q000502:physiology; D014945:Wound Healing / Q000502:physiology; D000097794:Kalinin
D015815:Cell Adhesion Molecules; D039201:Integrin alpha3beta1; D000097794:Kalinin