THE PERSISTENT ACTIVATION MECHANISM OF TGF-b IN PROGRESSIVE GLOMERULAR DISEASES

进展性肾小球疾病中TGF-b的持续激活机制

基本信息

批准号：
06671143
负责人：
OKUDA Seiya
金额：
$ 1.41万
依托单位：
KYUSHU UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1994
资助国家：
日本
起止时间：
1994 至 1995
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-06671143/
关键词：
Growth factor TGF-b TGF-b binding protein Glomerulosclerosis Interstitial fibrosis matrix TGF-b localization TGF-b acctivation LTBP PCR 尿細管細胞

项目摘要

TGF-beta1 has been shown to play an important role in maintaining the renal histological structure as well as the glomerular and tubular functions. TGF-beta1 is usually secreted by normal cells in a biologically inactive or latent form with a high molecular weight. The latent form of TGF-beta1 may have two different structures of large latent TGF-beta1 with LTBP and small latent TGF-beta1 without LTBP.LTBP plays a central role in the assembly, secretion, activation and localization of TGF-beta1. In the present study, we investigated which renal cells produce large or small latent TGF-beta1 and also tried to determine the precise localization of TGF-beta1 protein in the kidney of normal rats or adriamycin-induced FGS model rats, using RT-PCR,in situ hybridization and immunohistochemistory. In the normal kidney. TGF-beta1 mRNA was detected in all nephron segments and glomeruli. On the other hand, LTBP mRNA was present only in the glomeruli, while it was absent in every segment of the renal tubules. This finding suggested that the tubular cells secrete small latent TGF-beta1, while glomerular cells secrete large latent TGF-beta1. In the diseased kidney, a TGF-beta bioassay revealed a progressive increase in latent TGF-beta1 secretion from cultured renal tissues. The tubular cells also began to secrete large latent TGF-beta1, which closely paralleled the degree of the tubulointerstitial changes. The increased amount of large latent TGF-beta was localized in the sclerotic and fibrotic tissue in association with the extracellular matrix (ECM). In conclusion, the tubular cells might thus turn out to be a source of large latent TGF-beta1 in progressive process of this model, while matrix-associated large latent TGF-beta1 may play an important role in the ECM metabolism of either sclerotic or fibrotic lesions.

TGF-BETA1已被证明在维持肾脏组织学结构以及肾小球和管状功能方面起着重要作用。 TGF-BETA1通常由正常细胞以高分子量的生物学无活性或潜在形式分泌。 TGF-BETA1的潜在形式可能具有具有LTBP的大型潜在TGF-BETA1的两种不同的结构，而没有LTBP.LTBP的小潜在TGF-BETA1在TGF-BETA1的组装，分泌，激活和定位中起着核心作用。在本研究中，我们研究了哪些肾细胞会产生大或小潜在的TGF-BETA1，还试图确定在正常大鼠的肾脏中TGF-BETA1蛋白的精确定位，或使用RT-PCR在正常大鼠的肾脏或Adriamycin诱导的FGS模型大鼠中，现场杂交和免疫组织化学构成。在普通肾脏中。在所有肾单位段和肾小球中都检测到TGF-BETA1 mRNA。另一方面，LTBP mRNA仅存在于肾小球中，而在肾小管的每个段中都不存在。这一发现表明，管状细胞分泌小潜在的TGF-BETA1，而肾小球细胞分泌大型潜在的TGF-BETA1。在患病的肾脏中，TGF-beta生物测定显示培养的肾脏组织的潜在TGF-BETA1分泌逐渐增加。管状细胞还开始分泌大型潜在的TGF-BETA1，这与肾小管间隙变化的程度紧密相似。与细胞外基质（ECM）相关的硬化性和纤维化组织中，大量潜在的TGF-β量增加位于硬化和纤维化组织中。总之，因此，管状细胞可能是该模型进行性过程中的大型潜在TGF-BETA1的来源，而基质相关的大型潜在TGF-BETA1可能在ECM的孢子菌病或纤维化病变的ECM代谢中起重要作用。