title: Genetic deficiency of adiponectin protects against acute kidney injury.
abstract: Adiponectin is a multifunctional cytokine that has a role in regulating inflammation. Here we determined whether adiponectin modulates ischemic acute kidney injury. Compared with wild-type mice, adiponectin-knockout mice were found to have lower serum creatinine and less tubular damage or apoptosis following ischemia/reperfusion injury. This latter process was associated with decreased Bax and reduced activation of p53 and caspase-3. Targeted disruption of adiponectin was also found to inhibit the infiltration of neutrophils, macrophages, and T cells into the injured kidneys. This was associated with inhibition of NF-κB activation and reduced expression of the proinflammatory molecules IL-6, TNF-α, MCP-1, and MIP-2 in the kidney after ischemia/reperfusion injury. Wild-type mice engrafted with adiponectin-null bone marrow had less kidney dysfunction and tubular damage than adiponectin-null mice engrafted with wild-type bone marrow. Conversely, adiponectin-null mice engrafted with wild-type bone marrow had similar renal dysfunction and tubular damage compared with wild-type mice engrafted with wild-type bone marrow. In cultured macrophages, adiponectin directly promoted macrophage migration: a process blocked by the PI3 kinase inhibitor, LY294002. Thus, our results show that adiponectin has a pivotal role in the pathogenesis of acute renal ischemia/reperfusion injury and may be a potential therapeutic target.
authors.affiliation: Division of Nephrology, Department of Medicine, Baylor College of Medicine, Houston, Texas 77030, USA.
authors.forename: Xiaogao
authors.initials: X
authors.lastname: Jin
authors.forename: Jiyuan
authors.initials: J
authors.lastname: Chen
authors.forename: Zhaoyong
authors.initials: Z
authors.lastname: Hu
authors.forename: Lawrence
authors.initials: L
authors.lastname: Chan
authors.forename: Yanlin
authors.initials: Y
authors.lastname: Wang
mesh_terms: D058186:Acute Kidney Injury / Q000097:blood / Q000235:genetics / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D052242:Adiponectin / Q000172:deficiency* / Q000235:genetics; D000818:Animals; D017209:Apoptosis; D016026:Bone Marrow Transplantation; D053148:Caspase 3 / Q000378:metabolism; D018932:Chemokine CCL2 / Q000378:metabolism; D054426:Chemokine CXCL2 / Q000378:metabolism; D003404:Creatinine / Q000097:blood; D004195:Disease Models, Animal; D004789:Enzyme Activation; D018836:Inflammation Mediators / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D007668:Kidney / Q000187:drug effects / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D008264:Macrophages / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016328:NF-kappa B / Q000378:metabolism; D020556:Neutrophil Infiltration; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D015427:Reperfusion Injury / Q000097:blood / Q000235:genetics / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D013601:T-Lymphocytes / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D052242:Adiponectin; C499919:Adipoq protein, mouse; C494827:Bax protein, mouse; C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D054426:Chemokine CXCL2; C404915:Cxcl2 protein, mouse; D018836:Inflammation Mediators; D015850:Interleukin-6; D016328:NF-kappa B; D000081082:Phosphoinositide-3 Kinase Inhibitors; D047428:Protein Kinase Inhibitors; D014409:Tumor Necrosis Factor-alpha; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; D003404:Creatinine; D058539:Phosphatidylinositol 3-Kinase; C505409:Casp3 protein, mouse; D053148:Caspase 3