| Autor: |
Liu, Ning, Makino, Toshiaki, Nogaki, Fumiaki, Kusano, Hitoshi, Suyama, Katsuo, Muso, Eri, Honda, Gisho, Kita, Toru, Ono, Takahiko |
| Předmět: |
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| Zdroj: |
American Journal of Physiology: Renal Physiology; Oct2004, Vol. 56 Issue 4, pF612-F620, 9p, 17 Color Photographs, 16 Graphs |
| Abstrakt: |
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)-β 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 antibodyinjected group. Northern blot analysis revealed that factor V mRNA expression was prominent on day 3 and was weak on day 8. Doublelabeling experiments revealed the frequent colocalization of α-smooth muscle actin with factor V, FRA, and fibronectin in the same mesangial areas of glomeruli. TGF-β, 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-β and CTGF in MsPGN. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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