ROLE OF AND REGULATION OF GROWTH FACTOR TGF-β IN GLOMERULAR LESIONS

转化生长因子-β2型受体胞外区可与活性转化生长因子-β紧密结合，但不参与转化生长因子-β的信号转导。因此，大量的转化生长因子-β可溶性受体可以阻止转化生长因子-β与真正的转化生长因子-β受体结合。为探讨转化生长因子-β可溶性受体在体内对转化生长因子-β作用的影响，在单侧输尿管梗阻前1d，用5×10~(-8)重组腺病毒载体将转化生长因子-β2型受体胞外区基因导入大鼠肌肉。用双抗体夹心ELISA法测定血清转化生长因子-β可溶性受体浓度。转染后第10天血清中可溶性受体浓度为70 ng/ml，是报道的大鼠血清中活性形式转化生长因子-β浓度的50倍，被认为足以在体内阻断活性转化生长因子-β。输尿管梗阻大鼠肾小管损伤和间质纤维化明显。这些损伤通过转化生长因子-β可溶性受体水平的升高而减轻。转化生长因子-β可溶性受体基因可显著减少间质纤维连接蛋白积聚、波形蛋白表达和巨噬细胞积聚。转化生长因子-β2型可溶性受体是转化生长因子-β调节肾纤维化的有效抑制剂。

The extracellular domain of TGF-β type 2 receptor can bind active TGF-β tightly but does not involve signal transduction of TGF-β. Therefore, a large amount of TGF-β soluble receptor can prevent TGF-β binding to true TGF-β receptor. To investigate the effects of TGF-β soluble receptor on TGF-β action in vivo, the gene of TGF-β type 2 receptor extracellular domain was transfected into the muscle of rats by using 5x10^8 recombinant adenovirus vector at 1 days before the unilateral uretal obstruction. Serum concentration of TGF-β soluble receptor was quantitated by ELISA assay. The serum concentration of the soluble receptor at 10 days after the transfection was 70ng/ml, which was 50-fold higher than reported concentration of active form TGF-β in rats serum and considered to be sufficient to block the active TGF-β in vivo. Tubular damage and interstitial fibrosis were marked in ureteral obstruction rat kidney. These lesions were attenuated by the elevated level of the TGF-β soluble receptor. Interstitial fibronectin accumulation, vimentin expression and macrophage accumulation were markedly decreased by the TGF-β soluble receptor gene tranfection. TGF-β type 2 soluble receptor is a potent inhibitor of TGF-β to modulate renal fibrosis.