Astragaloside IV attenuates renal tubulointerstitial fibrosis by inhibiting p38 MAPK signaling |
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Authors: | Xu Weijia Shao Xinghua Xu Xiaoping Yao Jufang Wang Qin Zhang Minfang Wang Ling Tian Lei Mou Shan Ni Zhaohui. |
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Affiliation: | *Department of Nephrology, Molecular Cell Laboratory for Kidney Disease, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200001, China;Corresponding author: Mou Shan, Email: shanmou_renji@126.com |
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Abstract: | Objective To investigate the effect of astragaloside IV (AS-IV) on renal tubulointerstitial fibrosis and its regulation on p38 MAPK signaling. Methods In vivo, UUO model with renal tubulointerstitial injury was constructed. Mice in AS-IV group were orally administrated AS-IV 20 mg•kg-1•d-1 for 7 days after operation, and mice in other groups were administrated the equal volume vehicle. Bilateral kidneys were collected in 7 and 14 days after operation. Transverse kidney slices were stained with Masson trichrome to evaluate the severity of renal tubule injury. In vitro, normal human renal tubular epithelial cells (HK-2) were stimulated with recombinant TGF-β1 (10 ng/ml) and simultaneously treated with different concentrations of AS-IV (0, 50, 100, 200 μg/ml) for 24 h. SB203580 (10 μmol/L) was also ultilized to pre-treat HK-2 cells for 1 h to inhibit phosphorylation of p38 MAPK signaling. The expression of FN, Col IV, and α-SMA were investigated by western blotting and real-time PCR. The expression of p-p38 MAPKs were also observed by Western Blotting. Results Astragaloside IV morphologically ameliorated renal tubulointerstitial fibrosis. The proteins and mRNA expression of FN, Col IV, α-SMA, and TGF-β1 were also increased significantly in UUO kidney tissues (all P<0.05), which could be reversed by AS-IV administration (all P<0.05). In vitro, the expression of FN, Col IV, and α-SMA were up-regulated by TGF-β1 after stimulating for 24 h (all P<0.05), which were decreased by AS-IV. The inhibition effect on FN and α-SMA were similar between AS-IV and MAPK inhibitor SB203580. AS-IV inhibited p-p38 MAPK signals both in vivo and in vitro. Conclusions AS-IV could attenuate renal tubulointerstitial fibrosis induced by UUO and TGF-β1 through reducing FN、Col IV、α-SMA expression in renal tubular cells. The mechanism of AS-IV protective effect might be associated with inhibition of p38 MAPK phosphorylation. |
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