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Genetic deficiency of adiponectin protects against acute kidney injury
Adiponectin is a multifunctional cytokine that has a role in regulating inflammation. Here we determined if 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 follo...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3612389/ https://www.ncbi.nlm.nih.gov/pubmed/23302722 http://dx.doi.org/10.1038/ki.2012.408 |
Sumario: | Adiponectin is a multifunctional cytokine that has a role in regulating inflammation. Here we determined if 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 an 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 to 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 plays a pivotal role in the pathogenesis of acute renal ischemia/reperfusion injury and may be a potential therapeutic target. |
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