Renal expression of transforming growth factor-β inducible gene-h3 (βig-h3) in normal and diabetic rats
Renal expression of transforming growth factor-β inducible gene-h3 (βig-h3) in normal and diabetic rats
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DOI：
10.1046/j.1523-1755.1998.00081.x
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发表时间：
1998-10-01
影响因子：
19.6
通讯作者：
Cooper, ME
中科院分区：
文献类型：
--
作者：
Gilbert, RE;Wilkinson-Berka, JL;Cooper, ME
背景转化生长因子-β（TGF-β）与许多以肾小球硬化和肾小管间质纤维化为特征的肾脏疾病的发病机制有关。TGF-β以潜伏形式分泌，需要细胞外修饰以变得具有生物活性。TGF-β-inducible gene-h3（beta ig-h3）是最近发现的一种TGF-β诱导的基因产物。本研究旨在检测β ig-h3在正常和糖尿病大鼠中的表达。通过北方印迹分析和原位杂交在20只Sprague道利大鼠中评估β ig-h 3、TGF-β 1和α 1（IV）胶原基因表达，随机分配接受链脲佐菌素（糖尿病，N = 11）或单独柠檬酸盐缓冲液（对照）。N = 9），并在8个月后处死。外源性TGF-β 1对β ig-h3表达的影响也在培养的近端肾小管细胞中进行了评估。原位杂交将β ig-h3基因表达定位于对照组和糖尿病动物近端小管的近球器和直部（S3段）。肾脏TGF-β 1。与对照组相比，糖尿病大鼠的β ig-h3和α 1（IV）胶原mRNA增加了两到三倍（P < 0.01）。糖尿病大鼠肾脏TGF-β 1和β ig-h3基因表达呈显著相关（r = 0.73，P = 0.01）。此外，在培养的近端肾小管细胞中，外源性TGF-β 1以剂量依赖的方式刺激β ig-h3 mRNA表达增加。这些发现支持了生物活性TGF-β在糖尿病肾病中起致病作用的假设，并表明β ig-h3可能是肾脏中TGF-β 1生物活性的有用指标。
Background. Transforming growth factor-beta (TGF-beta) has been implicated in the pathogenesis of a number of kidney diseases characterized by glomerulosclerosis and tubulointerstitial fibrosis. TGF-beta is secreted in a latent form requiring extracellular modification to become biologically active. TGF-beta-inducible gene-h3 (beta ig-h3) is a recently identified TGF-beta-induced gene product. The present study sought to examine beta ig-h3 expression in normal and diabetic rats.Methods. beta ig-h3, TGF-beta 1 and alpha 1 (IV) collagen gene expression were assessed by Northern blot analysis and in situ hybridization in 20 Sprague Dawley rats, randomly assigned to receive streptozotocin (diabetic, N = 11) or citrate buffer alone (control. N = 9) and sacrificed eight months later. The effect of exogenous TGF-beta 1 on beta ig-h3 expression was also assessed in cultured proximal tubular cells.Results. In situ hybridization localized beta ig-h3 gene expression to the juxtaglomerular apparatus and the pars recta (S3 segment) of proximal tubules in both control and diabetic animals. Kidney TGF-beta 1. beta ig-h3 and alpha 1 (IV) collagen mRNA from diabetic rats were increased two- to threefold compared with controls (P < 0.01). There was a significant correlation between TGF-beta 1 and beta ig-h3 gene expression in kidneys from diabetic rats (r = 0.73, P = 0.01). In addition, beta ig-h3 mRNA increased in response to exogenous TGF-beta 1 in a dose-dependent fashion in cultured proximal tubular cells.Conclusion. These findings support the hypothesis that biologically active TGF-beta plays a pathogenetic role in diabetic kidney disease and suggest that beta ig-h3 may be a useful index of TGF-beta 1 bioactivity in the kidney.