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
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DOI：
10.1152/ajprenal.00322.2003
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发表时间：
2004-10-01
影响因子：
4.2
通讯作者：
Ono, T
中科院分区：
文献类型：
--
作者：
Liu, N;Makino, T;Ono, T
众所周知，组织因子启动外源性凝血途径，将因子X激活为Xa，而因子V是膜结合的有效辅助因子，用于因子Xa激活凝血酶原的终止阶段。在先前的体外研究中，通过炎症刺激在培养的系膜细胞中诱导了因子V，并且因子V表达的增加促进了培养的系膜细胞表面上纤维蛋白的生成。我们报告说，在系膜增生性肾炎（MsPGN）中，通过因子 V 的表达，细胞外基质（ECM）的积累与系膜区域的凝血相关。 Wistar大鼠静脉注射兔抗大鼠胸腺细胞血清，同时注射或不注射兔抗因子V抗体。免疫组织化学时程研究显示，因子V表达在第3天显着，纤维蛋白相关抗原（FRA）沉积，然后是ECM积累，从第3天到第8天。疾病对照组的肾小球中也观察到大量纤连蛋白沉积和转化生长因子（TGF）-β表达，明显高于正常组，并且这些沉积和表达在抗因子V中和抗体注射组中显着减少。 Northern 印迹分析显示，第 3 天，V 因子 mRNA 表达显着，第 8 天较弱。双标记实验显示，α-平滑肌肌动蛋白与 V 因子、FRA 和纤连蛋白频繁共定位于肾小球的同一系膜区域。疾病对照组中 TGF-β、结缔组织生长因子 (CTGF)、IV 型胶原和纤连蛋白 mRNA 上调，注射抗 V 因子中和抗体可抑制肾小球中这些 mRNA 的表达。目前的结果表明，ECM 成分的积累可能通过 MsPGN 中系膜因子 V 的表达以及 TGF-β 和 CTGF 的上调表达，与系膜区域的凝血一致。
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)-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.