Genetic deficiency of adiponectin protects against acute kidney injury

作者：Jin Xiaogao; Chen Jiyuan; Hu Zhaoyong; Chan Lawrence; Wang Yanlin^*

来源：Kidney International, 2013, 83(4): 604-614.

DOI：10.1038/ki.2012.408

• apoptosis
• inflammation
• ischemia-reperfusion injury
• p53
• PI3 kinase
• NF-kappa B

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-kappa B activation and reduced expression of the proinflammatory molecules IL-6, TNF-alpha, 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. Kidney International (2013) 83, 604-614; doi:10.1038/ki.2012.408; published online 9 January 2013

• 出版日期2013-4