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This Article Full Text Full Text (PDF) All Versions of this Article: 287/4/F612    most recent 00322.2003v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via ISI Web of Science (3) Citing Articles via Google Scholar Google Scholar Articles by Liu, N. Articles by Ono, T. Search for Related Content PubMed PubMed Citation Articles by Liu, N. Articles by Ono, T.

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

¹Division of Nephrology, Department of Cardiovascular Medicine and ²Department of Pharmacognosy, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto 606-8507; and ³Division of Nephrology, Kitano Hospital, Tazuke-Kofukai Foundation Medical Research Institute, Osaka 530-0026, Japan

Submitted 5 September 2003 ; accepted in final form 27 May 2004

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 promoted 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)- 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 -smooth muscle actin with factor V, FRA, and fibronectin in the same mesangial areas of glomeruli. TGF-, 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- and CTGF in MsPGN.

experimental glomerulonephritis; extracellular matrix components accumulation; transforming growth factor-; connective tissue growth factor