EXPRESSION OF TRANSFORMING GROWTH-FACTOR-BETA IS ELEVATED IN HUMAN AND EXPERIMENTAL DIABETIC NEPHROPATHY
EXPRESSION OF TRANSFORMING GROWTH-FACTOR-BETA IS ELEVATED IN HUMAN AND EXPERIMENTAL DIABETIC NEPHROPATHY
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DOI：
10.1073/pnas.90.5.1814
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发表时间：
1993-03-01
影响因子：
11.1
通讯作者：
BORDER, WA
中科院分区：
文献类型：
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作者：
YAMAMOTO, T;NAKAMURA, T;BORDER, WA
糖尿病现在是导致进行性肾功能衰竭的最常见原因，导致透析或移植。糖尿病肾病的主要病理特征是细胞外基质在肾小球内积聚。糖尿病环境中导致细胞外基质堆积的因素尚不清楚。在此，我们报道了糖尿病大鼠肾小球中转化生长因子-β(转化生长因子-β)mRNA和蛋白的表达缓慢递增。转化生长因子-β的一个关键作用是诱导细胞外基质的产生，已知的由转化生长因子-β诱导的特定基质蛋白在糖尿病大鼠肾小球中增加。这些蛋白质包括纤维连接蛋白、肌腱蛋白和蛋白多糖二聚糖的选择性剪接形式。转化生长因子-β此前并未涉及糖尿病肾脏中的基质堆积。糖尿病肾病患者的肾小球也显示出免疫反应阳性的转化生长因子-β蛋白和特殊形式的纤维连接蛋白的沉积显著增加，而正常人或其他肾小球疾病患者的肾小球(细胞外基质堆积不是特征)的肾小球呈阴性或勉强阳性。这些结果提示转化生长因子-β在糖尿病肾病的发病机制中起重要作用。
Diabetes is now the most common cause of progressive kidney failure leading to dialysis or transplantation. The central pathological feature of diabetic nephropathy is accumulation of extracellular matrix within the glomeruli. The factors in the diabetic milieu responsible for extracellular matrix accumulation are not understood. Here we report that in glomeruli of rats made diabetic there is a slow, progressive increase in the expression of transforming growth factor beta (TGF-beta) mRNA and TGF-beta protein. A key action of TGF-beta is induction of extracellular matrix production, and specific matrix proteins known to be induced by TGF-beta were increased in diabetic rat glomeruli. These proteins include an alternatively spliced form of fibronectin, tenascin, and the proteoglycan biglycan. TGF-beta has not previously been implicated in the matrix accumulation that occurs in the diabetic kidney. Glomeruli from humans with diabetic nephropathy also showed a striking increase in immunoreactive TGF-beta protein and deposition of the special form of fibronectin, whereas glomeruli from normal subjects or from individuals with other glomerular diseases (where extracellular matrix accumulation is not a feature) were negative or barely positive. These results implicate TGF-beta in the pathogenesis of diabetic nephropathy.