REGULATION OF TGF-beta ACTIVITY FOR ATTENUATION OF GLOMERULAR LESIONS

1. TGF-β的潜伏期与肾脏疾病的慢性化我们前期的研究表明，在慢性肾脏疾病模型中，大部分TGF-β没有被激活，而是以潜伏形式存在于组织中。潜伏性TGF-β的组织储存对于组织学变化的慢性化可能是重要的。在体外和体内检查了潜伏性TGF-β的组织定位。来自系膜细胞培养物的基质显示含有大量潜伏的TGF-β。在实验性FGS模型中，潜伏的TGF-β广泛地积聚在硬化性肾小球和纤维性肾小球中，并与其他基质蛋白共存。基质相关的潜在TGF-β可能作为一种慢性刺激物驱动新的ECM合成，这对于维持和发展硬化或纤维化组织都是重要的。2. TGF-β可溶性受体在肾纤维化中的作用TGF-β可溶性受体是TGF-β 2型受体的细胞外结构域，预期其在肾脏疾病中抑制TGF-β的作用。用腺病毒载体将可溶性受体基因转染到单侧输尿管梗阻大鼠肌肉中。间质纤维化减轻与可溶性受体的血清水平的增加有关。TGF-β可溶性受体是TGF-β的有效抑制剂，以调节肾组织学病变。

1.The latency of TGF-beta and chronicity of renal diseasesOur previous studies demonstrated that in a chronic renal disease model, most of TGF-beta is not activated and exsits as a latent form in tissue. The tissue storage of latent TGF-beta may be important for chronicity of histological changes. Tissue localization of latent TGF-beta was examined in vitro and in vivo. The matrices from mesangial cell cultures were shown to contain a large amount of latent TGF-beta. In an experimental FGS model, latent TGF-beta accumulates in the sclerosing glomeruli and the fibrous interstitium extensively and coexists with the other matrix proteins. The matrix-associated latent TGF-beta may serve as a chronic stimulus driving new ECM synthesis, which is important for both keeping and developing sclerosis or fibrotic tissues.2.The effect of TGF-beta soluble receptor on renal fibrosisThe TGF-beta soluble receptor, which is extracellular domain of TGF-beta type 2 receptor has been expected to inhibit TGF-beta action in renal diseases. The gene of the soluble receptor was transfectd to muscle in rats with unilateral ureter obstruction, using adenovirus vectors. The interstitial fibrosis was attenuated in association with the increased serum levels of the soluble receptor. TGF-beta soluble receptor is a potent inhibitor of TGF-beta to modulate renal histological lesions.