title: Role of surfactant proteins A and D in sepsis-induced acute kidney injury.
abstract: Sepsis is a major cause of acute kidney injury (AKI) with high rates of morbidity and mortality. Surfactant proteins A and D (SP-A, SP-D) play a critical role in host defense and regulate inflammation during infection. Recent studies indicate SP-A and SP-D are expressed in the kidney. The current study examines the role of SP-A and SP-D in the pathogenesis of sepsis-induced AKI. Wild-type (WT) and SP-A/SP-D double-knockout (KO) C57BL/6 mice were treated by cecal ligation and puncture (CLP) or sham surgery. Histological, cellular, and molecular indices of kidney injury were investigated in septic mice 6 and 24 h after CLP. Twenty-four hours after CLP, kidney injury was more severe, renal function was decreased, and blood creatinine and blood urea nitrogen were higher in septic SP-A/SP-D KO mice (P < 0.05, versus septic WT mice). Kidney edema and vascular permeability were increased in septic SP-A/SP-D KO mice (P < 0.01, versus septic WT mice). Apoptotic cells increased significantly (P < 0.01) in the kidney of septic SP-A/SP-D KO mice compared with septic WT mice. Molecular analysis revealed levels of Bcl-2 (an inhibitor of apoptosis) were lower and levels of caspase 3 (a biomarker of apoptosis) were higher in the kidney of septic SP-A/SP-D KO mice (P < 0.01, versus septic WT mice). Furthermore, levels of nuclear factor κB and phosphorylated IκB-α increased significantly in the kidney of septic SP-A/SP-D KO mice compared with septic WT mice, suggesting SP-A/SP-D KO mice have a more pronounced inflammatory response to sepsis. We conclude SP-A and SP-D attenuate kidney injury by modulating inflammation and apoptosis in sepsis-induced AKI.
authors.affiliation: *Department of Surgery, SUNY Upstate Medical University, Syracuse, New York; †Department of Critical Care Medicine, Wuhan University, Renmin Hospital, Wuhan, Hubei Province, People's Republic of China.
authors.forename: Jiao
authors.initials: J
authors.lastname: Liu
authors.forename: Osama
authors.initials: O
authors.lastname: Abdel-Razek
authors.forename: Zhiyong
authors.initials: Z
authors.lastname: Liu
authors.forename: Fengqi
authors.initials: F
authors.lastname: Hu
authors.forename: Qingshan
authors.initials: Q
authors.lastname: Zhou
authors.forename: Robert N
authors.initials: RN
authors.lastname: Cooney
authors.forename: Guirong
authors.initials: G
authors.lastname: Wang
mesh_terms: D058186:Acute Kidney Injury / Q000209:etiology / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D017209:Apoptosis / Q000235:genetics; D002199:Capillary Permeability / Q000235:genetics; D003404:Creatinine / Q000097:blood; D004195:Disease Models, Animal; D018345:Mice, Knockout; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D037662:Pulmonary Surfactant-Associated Protein A / Q000235:genetics / Q000378:metabolism*; D037701:Pulmonary Surfactant-Associated Protein B / Q000235:genetics / Q000378:metabolism*; D018805:Sepsis / Q000150:complications / Q000235:genetics / Q000378:metabolism* / Q000473:pathology
chemical_list: D016328:NF-kappa B; D019253:Proto-Oncogene Proteins c-bcl-2; D037662:Pulmonary Surfactant-Associated Protein A; D037701:Pulmonary Surfactant-Associated Protein B; C052617:Bcl2 protein, mouse; D003404:Creatinine