title: Autophagy is activated to protect against podocyte injury in adriamycin-induced nephropathy.
abstract: Podocytes are highly differentiated epithelial cells wrapping glomerular capillaries to form the filtration barrier in kidneys. As such, podocyte injury or dysfunction is a critical pathogenic event in glomerular disease. Autophagy plays an important role in the maintenance of the homeostasis and function of podocytes. However, it is less clear whether and how autophagy contributes to podocyte injury in glomerular disease. Here, we have examined the role of autophagy in adriamycin-induced nephropathy, a classic model of glomerular disease. We show that autophagy was induced by adriamycin in cultured podocytes in vitro and in podocytes in mice. In cultured podocytes, activation of autophagy with rapamycin led to the suppression of adriamycin-induced apoptosis, whereas inhibition of autophagy with chloroquine enhanced podocyte apoptosis during adriamycin treatment. To determine the role of autophagy in vivo, we established an inducible podocyte-specific autophagy-related gene 7 knockout mouse model (Podo-Atg7-KO). Compared with wild-type littermates, Podo-Atg7-KO mice showed higher levels of podocyte injury, glomerulopathy, and proteinuria during adriamycin treatment. Together, these observations support an important role of autophagy in protecting podocytes under the pathological conditions of glomerular disease, suggesting the therapeutic potential of autophagy induction.
authors.affiliation: Department of Nephrology, Second Xiangya Hospital, Central South University, Changsha, Hunan, China.|Department of Cellular Biology and Anatomy, Medical College of Georgia at Augusta University and Charlie Norwood Veterans Affairs Medical Center, Augusta, Georgia; and.
authors.forename: Mixuan
authors.initials: M
authors.lastname: Yi
authors.affiliation: Department of Nephrology, Second Xiangya Hospital, Central South University, Changsha, Hunan, China.|Department of Cellular Biology and Anatomy, Medical College of Georgia at Augusta University and Charlie Norwood Veterans Affairs Medical Center, Augusta, Georgia; and.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Nephrology, Second Xiangya Hospital, Central South University, Changsha, Hunan, China.|Department of Cellular Biology and Anatomy, Medical College of Georgia at Augusta University and Charlie Norwood Veterans Affairs Medical Center, Augusta, Georgia; and.
authors.forename: Yu
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Cellular Biology and Anatomy, Medical College of Georgia at Augusta University and Charlie Norwood Veterans Affairs Medical Center, Augusta, Georgia; and.
authors.forename: Man J
authors.initials: MJ
authors.lastname: Livingston
authors.affiliation: Department of Cellular Biology and Anatomy, Medical College of Georgia at Augusta University and Charlie Norwood Veterans Affairs Medical Center, Augusta, Georgia; and.
authors.forename: Jian-Kang
authors.initials: JK
authors.lastname: Chen
authors.affiliation: Department of Medicine, Medical College of Georgia at Augusta University and Charlie Norwood Veterans Affairs Medical Center, Augusta, Georgia.
authors.forename: N Stanley
authors.initials: NS
authors.lastname: Nahman
authors.affiliation: Department of Nephrology, Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors.forename: Fuyou
authors.initials: F
authors.lastname: Liu
authors.affiliation: Department of Nephrology, Second Xiangya Hospital, Central South University, Changsha, Hunan, China; zdong@augusta.edu.|Department of Cellular Biology and Anatomy, Medical College of Georgia at Augusta University and Charlie Norwood Veterans Affairs Medical Center, Augusta, Georgia; and.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Dong
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic; D017209:Apoptosis; D001343:Autophagy / Q000187:drug effects; D000071193:Autophagy-Related Protein 7 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D019610:Cytoprotection; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D050199:Podocytes / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D011507:Proteinuria / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D051436:Renal Insufficiency, Chronic / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D015398:Signal Transduction; D020123:Sirolimus / Q000494:pharmacology; D013997:Time Factors
chemical_list: D000903:Antibiotics, Antineoplastic; C502661:Atg7 protein, mouse; D004317:Doxorubicin; D000071193:Autophagy-Related Protein 7; D020123:Sirolimus
keywords: adriamycin; apoptosis; autophagy; kidney; mTOR; podocytes