AUTHOR=Chen Yan , Liu Qingpu , Shan Zengfu , Mi Wangyang , Zhao Yingying , Li Meng , Wang Baiyan , Zheng Xiaoke , Feng Weisheng 

TITLE=Catalpol Ameliorates Podocyte Injury by Stabilizing Cytoskeleton and Enhancing Autophagy in Diabetic Nephropathy

JOURNAL=Frontiers in Pharmacology

VOLUME=Volume 10 - 2019

YEAR=2019

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2019.01477

DOI=10.3389/fphar.2019.01477

ISSN=1663-9812

ABSTRACT=Catalpol, an iridoid glycoside extracted from Rehmannia glutinosa, has been found to ameliorate diabetic nephropathy (DN), but the mechanism has not been clarified. Podocyte injury play a key role in the pathogenesis of DN. This study mainly investigated the protective effect and potential mechanism of catalpol on podocyte injury of DN in vivo and in vitro. The results indicated that the pathological features of DN in mice were markedly ameliorated after treatment with catalpol. Moreover, podocyte foot process effacement, and down-regulation of nephrin and synaptopodin expression in DN mice were also remarkable reversed. In vitro, catalpol rescued disrupted cytoskeleton and increased migration ratio in podocyte induced by high glucose, the effect might be attributable to the inhibition of RhoA and Cdc42 activities but not Rac1. Furthermore, the impaired podocyte autophagy in DN mice was significantly enhanced after catalpol treatment. And catalpol also enhanced autophagy and lysosome biogenesis in cultured podocytes under high glucose condition. In addition, we confirmed that catalpol could inhibit mTOR activity and promote TFEB nuclear translocation in vivo and in vitro experiments. Our study demonstrated that catalpol could ameliorate podocyte injury in DN, and the protective effect of catalpol might result directly from the stabilization of podocyte cytoskeleton and the improvement of impaired podocyte autophagy.