NATURAL INHIBITOR OF TRANSFORMING GROWTH-FACTOR-BETA PROTECTS AGAINST SCARRING IN EXPERIMENTAL KIDNEY-DISEASE
NATURAL INHIBITOR OF TRANSFORMING GROWTH-FACTOR-BETA PROTECTS AGAINST SCARRING IN EXPERIMENTAL KIDNEY-DISEASE
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DOI：
10.1038/360361a0
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发表时间：
1992-11-26
期刊：
影响因子：
64.8
通讯作者：
RUOSLAHTI, E
中科院分区：
文献类型：
--
作者：
BORDER, WA;NOBLE, NA;RUOSLAHTI, E
导致肾功能衰竭的人类肾脏疾病的主要病理特征是细胞外基质在肾小球内的积聚。转化生长因子-β(转化生长因子-β)的过度表达是实验性肾小球肾炎病理基质堆积的基础。给肾小球肾炎大鼠注射抗转化生长因子-β抗体可抑制肾小球基质的产生，并防止基质在受损的肾小球中堆积。由转化生长因子-β诱导的基质成分之一--蛋白多糖核心蛋白能与转化生长因子-β结合并中和其生物学活性3，因此核心蛋白聚糖可能是转化生长因子-β的天然调节因子(参考文献3，4)。我们采用实验性肾小球肾炎模型1检测核心蛋白聚糖是否能在体内拮抗转化生长因子-β的作用。我们在此报道，核心蛋白聚糖的应用抑制了细胞外基质的增加，并减轻了疾病的表现，证实了我们的假设。根据我们的结果，核心蛋白聚糖可能最终被证明在临床上对与过度产生转化生长因子-β相关的疾病有用。
THE central pathological feature of human kidney disease that leads to kidney failure is the accumulation of extracellular matrix in glomeruli. Overexpression of transforming growth factor-beta (TGF-beta) underlies the accumulation of pathological matrix in experimental glomerulonephritis1. Administration of an antibody raised against TGF-beta to glomerulonephritic rats suppresses glomerular matrix production and prevents matrix accumulation in the injured glomeruli2. One of the matrix components induced by TGF-beta, the proteoglycan decorin, can bind TGF-beta and neutralize its biological activity3, so decorin may be a natural regulator of TGF-beta (refs 3, 4). We tested whether decorin could antagonize the action of TGF-beta in vivo using the experimental glomerulonephritis model1. We report here that administration of decorin inhibits the increased production of extracellular matrix and attenuates manifestations of disease, confirming our hypothesis. On the basis of our results, decorin may eventually prove to be clinically useful in diseases associated with overproduction of TGF-beta.