CTGF, a member of the CCN family of immediate early genes, is a recently discovered profibrotic growth factor, which is involved in many pathophysiologic procedures. CTGF acts as a downstream effector of TGF-β acting on interstitial cells to enhance the progression of fibrotic renal diseases. It has been shown that CTGF gene expression can be induced or blocked by some kinds of cytokine and drugs. It is an interesting candidate target for future intervention strategies of renal interstitial fibrosis. [
Astragalus mongholicus （AM） derived from the dry root ofAstragalus membranaceus Bge. var. mongolicus （Bge.） Hsiao is a widely used traditional Chinese medicine. The present study investigated the potential role of AM on renal fibrosis on a rat model of unilateral ureteral obstruction （UUO）. We divided 48 Sprague-Dawley rats randomly into 4 groups： sham-operated group （Sham）, untreated UUO group, AM-treated （10 g/（kg.d）） UUO group, and losartan-treated （20 mg/（kg.d）） UUO group as positive control. Haematoxylin ＆ eosin （HE） and Masson staining were used to study the dynamic histological changes of the kidneys 7 and 14 d after operation. The expressions of fibronectin （FN）, type I collagen （coil）, hepatocyte growth factor （HGF）, transforming growth factor-β1 （TGF-β1）, and eL-smooth muscle actin （α-SMA） were analyzed by real-time polymerase chain reaction （PCR）, immunohistochemistry staining, and Western blot. Results show that, similar to losartan, AM alleviated the renal damage and decreased the deposition of FN and coil from UUO by reducing the expressions of TGF-β1 and α-SMA （P〈0.05）, whereas HGF increased greatly with AM treatment （P〈0.05）. Our findings reveal that AM could retard the progression of renal fibrosis. The renoprotective effect of AM might be related to inhibition ofmyofibroblast activation, inducing of HGF and reducing of TGF-β1 expression.
Chuan ZUO Xi-sheng XIE Hong-yu QIU Yao DENG Da ZHU Jun-ming FAN
Total saponins of Panax notoginseng （PNS） have been shown to ameliorate renal interstitial fibrosis. Ginsenoside Rg 1, a panaxatriol saponin, is one of the major active molecules from PNS. The present study was undertaken to investigate the effect of ginsenoside Rgl on renal fibrosis in rats with unilateral ureteral obstruction （UUO）. The rats were randomly divided into 3 groups： sham-operation （n=15）, UUO （n=15） and UUO with ginsenoside Rgl treatment （n=15, 50 mg per kg body weight, intraperitoneally （i.p.） injected）. The rats were sacrificed on Days 7 and 14 after the surgery. Histological examination demonstrated that ginsenoside Rgl significantly inhibited interstitial fibrosis including tubular injury as well as collagen deposition, u-smooth muscle actin （α-SMA） and E-cadherin are two markers of tubular epithelial-myofibroblast transition （TEMT）. Interestingly, ginsenoside Rgl notably decreased α-SMA expression and simultaneously enhanced E-cadherin expression. The messenger RNA （mRNA） of transforming growth factor-β1 （TGF-β1）, a key mediator to regulate TEMT, in the obstructed kidney increased dramatically, but was found to decrease significantly after administration of ginsenoside Rg 1. Further study showed that ginsenoside Rgl considerably decreased the levels of both active TGF-β1 and phosphorylated Smad2 （pSmad2）. Moreover, ginsenoside Rgl substantially suppressed the expression of thrombospondin-1 （TSP-1）, a cytokine which can promote the transcription of TGF-β1 mRNA and the activation of latent TGF-β1. These results suggest that ginsenoside Rgl inhibits renal interstitial fibrosis in rats with UUO. The mechanism might be partly related to the blocking of TEMT via suppressing the expression of TSP-1.
Xi-sheng XIEMan YANGHeng-cuang LIUChuan ZUOZi LIYao DENGJun-ming FAN
