Chrysophanol ameliorates renal interstitial fibrosis by inhibiting the TGF-β/Smad signaling pathway

Biochemical Pharmacology
Fang DouAidong Wen

Abstract

Renal interstitial fibrosis (RIF) is a major pathological feature of chronic kidney disease at middle and end stages. Chrysophanol (CP), 1,8-dihydroxy-3-methyl-9,10-anthraquinone, is an anthraquinone isolated from Rheum palmatum L. with a variety of pharmacological activities including the suppression of RIF. However, the effect of CP on renal fibrosis and its potential mechanism have not been elucidated. We conducted a comprehensive study by determining the expression levels of fibrotic markers and proteins including TGF-β1, α-SMA, and Smad3 related to transforming growth factor-beta/Smad (TGF-β/Smad) pathway in unilateral ureteral obstruction (UUO) mice and TGF-β1-stimulated HK-2 cells with the treatment of CP using western blotting and RT-qPCR analyses. Using small interfering RNA and co-immunoprecipitation, we evaluated the influences of CP on the interactions between Smad3 and Smad7 proteins and also on TGF-β RI and TGF-βR II. We found that CP administration significantly ameliorated UUO-induced kidney damage by reversing abnormal serum and urine biochemical parameters and decreasing the production of fibrotic markers including collagen I, collagen III, fibronectin, and α-SMA. Our results showed that TGF-β1 and phospho-Sma...Continue Reading

Citations

Nov 26, 2020·Drug Design, Development and Therapy·Chuan GuoDehai Yin
Apr 16, 2021·Frontiers in Pharmacology·Mingming ZhaoYu Zhang
Aug 7, 2021·Advanced Drug Delivery Reviews·Huan XuLeaf Huang
Jan 1, 2022·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Guojing MaDifei Wang

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