title: Autophagy is activated to protect against endotoxic acute kidney injury.
abstract: Endotoxemia in sepsis, characterized by systemic inflammation, is a major cause of acute kidney injury (AKI) in hospitalized patients, especially in intensive care unit; however the underlying pathogenesis is poorly understood. Autophagy is a conserved, cellular catabolic pathway that plays crucial roles in cellular homeostasis including the maintenance of cellular function and viability. The regulation and role of autophagy in septic or endotoxic AKI remains unclear. Here we show that autophagy was induced in kidney tubular cells in mice by the endotoxin lipopolysaccharide (LPS). Pharmacological inhibition of autophagy with chloroquine enhanced LPS-induced AKI. Moreover, specific ablation of autophagy gene 7 (Atg7) from kidney proximal tubules worsened LPS-induced AKI. Together, the results demonstrate convincing evidence of autophagy activation in endotoxic kidney injury and support a renoprotective role of autophagy in kidney tubules.
authors.affiliation: Kidney Institute, Department of Nephrology, Shanghai Changzheng Hospital, Second Military Medical University, Shanghai, China.|Department of Cellular Biology and Anatomy, Medical College of Georgia, Georgia Regents University and Charlie Norwood VA Medical Center, Augusta, Georgia.
authors.forename: Shuqin
authors.initials: S
authors.lastname: Mei
authors.affiliation: Department of Cellular Biology and Anatomy, Medical College of Georgia, Georgia Regents University and Charlie Norwood VA Medical Center, Augusta, Georgia.
authors.forename: Man
authors.initials: M
authors.lastname: Livingston
authors.affiliation: Kidney Institute, Department of Nephrology, Shanghai Changzheng Hospital, Second Military Medical University, Shanghai, China.|Department of Cellular Biology and Anatomy, Medical College of Georgia, Georgia Regents University and Charlie Norwood VA Medical Center, Augusta, Georgia.
authors.forename: Jielu
authors.initials: J
authors.lastname: Hao
authors.affiliation: Kidney Institute, Department of Nephrology, Shanghai Changzheng Hospital, Second Military Medical University, Shanghai, China.|Department of Cellular Biology and Anatomy, Medical College of Georgia, Georgia Regents University and Charlie Norwood VA Medical Center, Augusta, Georgia.
authors.forename: Lin
authors.initials: L
authors.lastname: Li
authors.affiliation: Kidney Institute, Department of Nephrology, Shanghai Changzheng Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Changlin
authors.initials: C
authors.lastname: Mei
authors.affiliation: Department of Cellular Biology and Anatomy, Medical College of Georgia, Georgia Regents University and Charlie Norwood VA Medical Center, Augusta, Georgia.|Institute of Nephrology, The Second Xiangya Hospital, Central South University, Changsha, China.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Dong
mesh_terms: D058186:Acute Kidney Injury / Q000473:pathology* / Q000517:prevention & control; D000818:Animals; D001343:Autophagy / Q000187:drug effects / Q000502:physiology*; D000071193:Autophagy-Related Protein 7 / Q000235:genetics*; D002738:Chloroquine / Q000627:therapeutic use*; D002945:Cisplatin / Q000633:toxicity; D019446:Endotoxemia / Q000473:pathology*; D007687:Kidney Tubules, Proximal / Q000473:pathology*; D008070:Lipopolysaccharides / Q000633:toxicity*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D015427:Reperfusion Injury
chemical_list: C502661:Atg7 protein, mouse; D008070:Lipopolysaccharides; D002738:Chloroquine; D000071193:Autophagy-Related Protein 7; D002945:Cisplatin