Preparation and evaluation of anti-renal fibrosis activity of novel truncated TGF- receptor type II

Production of excessive transforming growth factor-beta 1 (TGF-1) with elevated TGF-1 activity has been implicated in renal fibrosis via renal epithelial cells activation and collagen deposition. As such, attenuating the binding of TGF-1 to its receptor TGF-beta receptor type II (TGF-RII) in TGF-1-dependent signaling is an attractive target for the control of renal fibrosis. Here, we verified the interaction between novel truncated human TGF-RII (thTRII, Thr23-Gln166) and TGF-1, prepared thTRII in Escherichia coli, and assessed the effects of thTRII on TGF-1-induced human kidney epithelial cells (HK-2) and unilateral ureteral obstruction (UUO) model of renal fibrosis. Our data showed that thTRII accounted for up to 20% of the total protein and 40% of the inclusion bodies of whole cell lysates under the optimal conditions (0.8 mM IPTG and 25 degrees C for 6 H). Most of the expressed protein in inclusion body was refolded by dialysis refolding procedures and purified by Ni2+-IDA affinity chromatography. Furthermore, thTRII decreased type I collagen and -smooth muscle actin protein expression in TGF-1-induced HK-2 cells, and ameliorated kidney morphology and fibrotic responses in fibrosis animal. These findings indicate that thTRII holds great promise for developing new treatments for renal fibrosis.