title: Autophagy attenuates diabetic glomerular damage through protection of hyperglycemia-induced podocyte injury.
abstract: Despite the recent attention focused on the important role of autophagy in maintaining podocyte homeostasis, little is known about the changes and mechanisms of autophagy in podocyte dysfunction under diabetic condition. In this study, we investigated the role of autophagy in podocyte biology and its involvement in the pathogenesis of diabetic nephropathy. Podocytes had a high basal level of autophagy. And basal autophagy inhibition either by 3-methyladenenine (3-MA) or by Beclin-1 siRNA was detrimental to its architectural structure. However, under diabetic condition in vivo and under high glucose conditions in vitro, high basal level of autophagy in podocytes became defective and defective autophagy facilitated the podocyte injury. Since the dynamics of endoplasmic reticulum(ER) seemed to play a vital role in regulating the autophagic flux, the results that Salubrinal/Tauroursodeoxycholic acid (TUDCA) could restore defective autophagy further indicated that the evolution of autophagy may be mediated by the changes of cytoprotective output in the ER stress. Finally, we demonstrated in vivo that the autophagy of podocyte was inhibited under diabetic status and TUDCA could improve defective autophagy. Taken together, these data suggested that autophagy might be interrupted due to the failure of ER cytoprotective capacity upon high glucose induced unmitigated stress, and the defective autophagy might accelerate the irreparable progression of diabetic nephropathy.
authors.affiliation: Center for Kidney Disease, 2nd Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu Province, China.
authors.forename: Li
authors.initials: L
authors.lastname: Fang
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhou
authors.forename: Hongdi
authors.initials: H
authors.lastname: Cao
authors.forename: Ping
authors.initials: P
authors.lastname: Wen
authors.forename: Lei
authors.initials: L
authors.lastname: Jiang
authors.forename: Weichun
authors.initials: W
authors.lastname: He
authors.forename: Chunsun
authors.initials: C
authors.lastname: Dai
authors.forename: Junwei
authors.initials: J
authors.lastname: Yang
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000235:genetics; D001343:Autophagy / Q000187:drug effects / Q000502:physiology*; D000071186:Beclin-1; D003928:Diabetic Nephropathies / Q000503:physiopathology*; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D006943:Hyperglycemia / Q000150:complications*; D051379:Mice; D050199:Podocytes / Q000473:pathology / Q000502:physiology*; D034741:RNA, Small Interfering / Q000235:genetics / Q000494:pharmacology; D013655:Taurochenodeoxycholic Acid / Q000494:pharmacology
chemical_list: D051017:Apoptosis Regulatory Proteins; D000071186:Beclin-1; C115010:Becn1 protein, mouse; D034741:RNA, Small Interfering; C025946:3-methyladenine; D013655:Taurochenodeoxycholic Acid; C031655:ursodoxicoltaurine; D000225:Adenine