Journal of the American Society of Nephrology, Vol 4, 1760-1770, Copyright © 1994 by American Society of Nephrology

REGULAR ARTICLES

Activation of procollagenase IV by cytochalasin D and concanavalin A in cultured rat mesangial cells: linkage to cytoskeletal reorganization

M Allenberg, T Weinstein, I Li and M Silverman
Department of Medicine, University of Toronto, Ontario, Canada.

The secretion and activation of procollagenase IV were studied in cultured rat mesangial cells. Under resting conditions, mesangial cells secrete predominantly a protein that, by gel zymography, exhibits gelatinase activity and also reacts with an anti-72-kd procollagenase IV antibody raised against a conserved region of the activation site of the enzyme. Cytochalasin D or concanavalin A treatment of mesangial cells causes disruption of actin stress fibers and results in the activation of procollagenase IV, yielding two lower molecular mass forms with gelatinase activity. Concanavalin A-induced actin filament disruption and procollagenase IV activation can be blocked by alpha- methyl-D-mannopyranoside but not by D(+)-galactose. Procollagenase IV as well as the activated forms all exhibit Ca2+ and Zn2+ dependency, characteristic of metalloproteinases. Mesangial cells in culture also secrete a specific tissue inhibitor of metalloproteinase, TIMP-2. Cytochalasin D treatment of mesangial cells reduces TIMP-2 expression. Cytochalasin D and concanavalin A both inhibited the serum-induced contraction of collagen gels embedded with mesangial cells. It was concluded that cytochalasin D-induced cytoskeletal disruption in mesangial cells may activate procollagenase IV by inhibiting TIMP-2 expression and that there is a concanavalin A-binding site on mesangial cells that is part of a transmembrane signaling system altering mesangial cell cytoskeletal organization and metalloproteinase secretion and activation.

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