title: Rhein Inhibits Autophagy in Rat Renal Tubular Cells by Regulation of AMPK/mTOR Signaling.
abstract: Rhubarb and its bioactive component rhein are frequently used for the treatment of chronic kidney diseases (CKD) in eastern Asia countries. However, the potential therapeutic mechanism remains unclear. Autophagy plays an important role in CKD. However, there were some important related issues that remained unresolved in the role of autophagy in CKD and treatment by rhubarb and rhein. We designed a number of experiments to examine whether rhubarb may reduce renal fibrosis and autophagy in rats with adenine (Ade)-induced renal tubular injury, and whether rhein could affect autophagic pathways in rat renal tubular cells. We found that, autophagic activation accompanied with renal fibrosis in rats with Ade-induced renal tubular injury, and both autophagy and renal fibrosis were attenuated by rhubarb. In addition, we observed that rhein could inhibit autophagy through regulating the key molecules in the AMPK-dependent mTOR signaling pathways, as well as the Erk and p38 MAPKs signaling pathways. These findings may partly explain the therapeutic mechanisms of rhubarb and rhein in treating CKD patients in clinic, and further suggest that targeting autophagy and related signaling pathways may provide new strategies for the treatment of renal fibrosis in CKD.
authors.affiliation: Department of Nephrology, The Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China.|Department of TCM Health Preservation, Second Clinic Medical School, Nanjing University of Chinese Medicine, Nanjng, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Tu
authors.affiliation: Center for Diabetes Care, Education and Research, Jiangsu Province Institute of Geriatrics, Nanjing, China.
authors.forename: Liubao
authors.initials: L
authors.lastname: Gu
authors.affiliation: Department of TCM Health Preservation, Second Clinic Medical School, Nanjing University of Chinese Medicine, Nanjng, China.
authors.forename: Diping
authors.initials: D
authors.lastname: Chen
authors.affiliation: Department of Traditional Chinese Medicine, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wu
authors.affiliation: First Clinic Medical School, Nanjing University of Chinese Medicine, Nanjng, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Nephrology, Huanggang Hospital of Traditional Chinese Medicine, Huanggang, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Hu
authors.affiliation: Department of Traditional Chinese Medicine, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China.
authors.forename: Yigang
authors.initials: Y
authors.lastname: Wan
authors.affiliation: Department of Nephrology, The Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Sun
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000818:Animals; D000880:Anthraquinones / Q000494:pharmacology*; D001343:Autophagy / Q000187:drug effects*; D002460:Cell Line; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005355:Fibrosis; D007668:Kidney / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D007687:Kidney Tubules, Proximal / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008517:Phytotherapy; D017207:Rats, Sprague-Dawley; D012250:Rheum / Q000737:chemistry; D015398:Signal Transduction / Q000187:drug effects*; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*
chemical_list: D000880:Anthraquinones; D004791:Enzyme Inhibitors; D058570:TOR Serine-Threonine Kinases; D055372:AMP-Activated Protein Kinases; C020491:rhein