title: Notoginsenoside R1 attenuates glucose-induced podocyte injury via the inhibition of apoptosis and the activation of autophagy through the PI3K/Akt/mTOR signaling pathway.
abstract: Injury to terminally differentiated podocytes contributes ignificantly to proteinuria and glomerulosclerosis. The aim of this study was to examine the protective effects of notoginsenoside R1 (NR1) on the maintenance of podocyte number and foot process architecture via the inhibition of apoptosis, the induction of autophagy and the maintenance pf podocyte biology in target cells. The effects of NR1 on conditionally immortalized human podocytes under high glucose conditions were evaluated by determining the percentage apoptosis, the percentage autophagy and the expression levels of slit diaphragm proteins. Our results revealed that NR1 protected the podocytes against high glucose-induced injury by decreasing apoptosis, increasing autophagy and by promoting cytoskeletal recovery. The phosphoinositide 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) signaling pathway was further investigated in order to elucidate the mechanisms responsible for the protective effects of NR1 on podocytes. Our data indicated that treatment with NR increased the phosphorylation levels of PI3K, Akt and mTOR, leading to the activation of the PI3K/Akt/mTOR signaling pathway in podocytes. To the best of our knowledge, this is the first in vitro study to demonstrate that NR1 protects podocytes by activating the PI3K/Akt/mTOR pathway.
authors.affiliation: Department of Nephrology, Ruikang Hospital Affiliated to Guangxi University of Chinese Medicine, Nanning, Guangxi 530011, P.R. China.
authors.forename: Guodong
authors.initials: G
authors.lastname: Huang
authors.affiliation: Department of Gynecology, Sichuan Academy of Medical Science and Sichuan Provincial People's Hospital, Chengdu, Sichuan 610072, P.R. China.
authors.forename: Bingyu
authors.initials: B
authors.lastname: Zou
authors.affiliation: School of Basic Medical Science, Guangxi University of Chinese Medicine, Nanning, Guangxi 530001, P.R. China.
authors.forename: Jianzhen
authors.initials: J
authors.lastname: Lv
authors.affiliation: School of Basic Medical Science, Guangxi University of Chinese Medicine, Nanning, Guangxi 530001, P.R. China.
authors.forename: Tongyu
authors.initials: T
authors.lastname: Li
authors.affiliation: Department of Biomedical Engineering, Medical School of University of Electronic Science and Technology of China, Chengdu, Sichuan 610054, P.R. China.
authors.forename: Guoli
authors.initials: G
authors.lastname: Huai
authors.affiliation: Department of Nephrology, Ruikang Hospital Affiliated to Guangxi University of Chinese Medicine, Nanning, Guangxi 530011, P.R. China.
authors.forename: Shaowei
authors.initials: S
authors.lastname: Xiang
authors.affiliation: School of Basic Medical Science, Guangxi University of Chinese Medicine, Nanning, Guangxi 530001, P.R. China.
authors.forename: Shilong
authors.initials: S
authors.lastname: Lu
authors.affiliation: Department of Nephrology, Ruikang Hospital Affiliated to Guangxi University of Chinese Medicine, Nanning, Guangxi 530011, P.R. China.
authors.forename: Huan
authors.initials: H
authors.lastname: Luo
authors.affiliation: Department of Nephrology, Ruikang Hospital Affiliated to Guangxi University of Chinese Medicine, Nanning, Guangxi 530011, P.R. China.
authors.forename: Yaping
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Center for Perinatal Research, Research Institute at Nationwide Children's Hospital, Columbus, OH 43215, USA.
authors.forename: Yi
authors.initials: Y
authors.lastname: Jin
authors.affiliation: Department of Biomedical Engineering, Medical School of University of Electronic Science and Technology of China, Chengdu, Sichuan 610054, P.R. China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Wang
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D015415:Biomarkers; D002460:Cell Line; D015870:Gene Expression; D036145:Ginsenosides / Q000494:pharmacology*; D005947:Glucose / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D050199:Podocytes / Q000187:drug effects* / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D036145:Ginsenosides; D005947:Glucose; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases; C072936:notoginsenoside R1