REGULATION OF TGF-β ACTIVITY FOR ATTENUATION OF GLOMERULAR LESIONS

The extracellular domain of TGF-β type 2 receptor can bind active TGF-β tightly but does not involvesignal transduction of TGF-β。Therefore，a large amount of TGF-β soluble receptor can prevent TGF-β binding to true TGF-β receptor. toinvestigate 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 byusing 5x10 - D18 - D1 recombinant adenovirus vector at 1 days before the unilateral uretalELISA assay. The Serum obstruction. Serum concentration of TGF-β soluble receptor was quantitatedconcentration 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 andconsidered to be sufficient to block the active TGF-β in体内。Tubular damage and interstitialfibrosis marked in ureteral obstruction rat kidney.这些课程由attenuated by theelevated level of the TGF-β soluble receptor. Interstitial fibronectin accumulation，vimentin表达式和macrophage accumulation were markedly decreased by TGF-β soluble receptorgene transfection. TGF-β type 2 soluble receptor is a potent inhibitor of TGF-βto modulate renalfibrosis。

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ィイD18ィエD1 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 TGF-β soluble receptor gene transfection. TGF-β type 2 soluble receptor is a potent inhibitor of TGF-βto modulate renal fibrosis.