期刊
KIDNEY INTERNATIONAL
卷 84, 期 1, 页码 90-103出版社
ELSEVIER SCIENCE INC
DOI: 10.1038/ki.2013.43
关键词
acute kidney injury; adenosine; apoptosis; inflammation; necrosis; transforming growth factor-beta 1
资金
- National Institutes of Health [GM-067081]
The volatile anesthetic isoflurane protects against renal ischemia and reperfusion injury by releasing renal tubular TGF-beta 1. As adenosine is a powerful cytoprotective molecule, we tested whether TGF-beta 1 generated by isoflurane induces renal tubular ecto-5'-nucleotidase (CD73) and adenosine to protect against renal ischemia and reperfusion injury. Isoflurane induced new CD73 synthesis and increased adenosine generation in cultured kidney proximal tubule cells and in mouse kidney. Moreover, a TGF-beta 1-neutralizing antibody prevented isoflurane-mediated induction of CD73 activity. Mice anesthetized with isoflurane after renal ischemia and reperfusion had significantly reduced plasma creatinine and decreased renal tubular necrosis, neutrophil infiltration, and apoptosis compared with pentobarbital-anesthetized mice. Isoflurane failed to protect against renal ischemia and reperfusion injury in CD73-deficient mice, in mice pretreated with a selective CD73 inhibitor, or in mice treated with an adenosine receptor antagonist. The TGF-beta 1-neutralizing antibody or the CD73 inhibitor attenuated isoflurane-mediated protection against HK-2 cell apoptosis. Thus, isoflurane causes TGF-beta 1-dependent induction of renal tubular CD73 and adenosine generation to protect against renal ischemia and reperfusion injury. Modulation of this pathway may have important therapeutic implications to reduce morbidity and mortality arising from ischemic acute kidney injury.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据