Coagulation in the mesangial area promotes ECM accumulation through factor V expression in MsPGN in rats

Coagulation in the mesangial area promotes ECM accumulation through factor V expression in MsPGN in rats. Am J Physiol Renal Physiol 287: F612-F620, 2004. First published June 1, 2004; 10.1152/ajprenal.00322.2003.--It is well known that tissue factor starts the extrinsic coagulation pathway, which activates factor X to Xa, and factor V is a membrane-bound potent cofactor for the terminating stage of prothrombin activation by factor Xa. In a previous in vitro study, factor V was induced in cultured mesangial cells by inflammatory, stimulation and increased expression of factor V pro-rooted fibrin generation on the cultured mesangial cell surface. We report that extracellular matrix (ECM) accumulation is increased in association with coagulation in the mesangial area through factor V expression in mesangioproliferative glomerulonephritis (MsPGN). Wistar rats were intravenously injected with rabbit anti-rat thymocyte serum accompanied with or without simultaneous injection of rabbit anti-factor V antibody. Time course study in immunohistochemistry revealed that factor V expression was prominent on day 3 and fibrin-related antigen (FRA) deposition, then ECM accumulation, followed from day 3 to day 8. Massive fibronectin depositions and transforming growth factor (TGF)-[beta] expression were also noted in glomeruli from the disease control group, markedly higher than those in the normal group, and these depositions and expressions were significantly decreased in the anti-factor V neutralizing antibody-injected group. Northern blot analysis revealed that factor V mRNA expression was prominent on day 3 and was weak on day 8. Double-labeling experiments revealed the frequent colocalization of [alpha]-smooth muscle actin with factor V, FRA, and fibronectin in the same mesangial areas of glomeruli. TGF-[beta], connective tissue growth factor (CTGF), collagen type IV, and fibronectin mRNA were upregulated in the disease control group, and anti-factor V-neutralizing antibody injection suppressed these mRNA expressions in glomeruli. The present results suggest that ECM components accumulation may progress in accordance with coagulation in the mesangial area through mesangial factor V expression and upregulated expression of TGF-[beta] and CTGF in MsPGN. experimental glomerulonephritis; extracellular matrix components accumulation; transforming growth factor-[beta]; connective tissue growth factor