The volatile anesthetic isoflurane induces ecto-5′-nucleotidase (CD73) to protect against renal ischemia and reperfusion injury

被引:53
作者
Kim, Mihwa [1 ]
Ham, Ahrom [1 ]
Kim, Joo Y. [1 ]
Brown, Kevin M. [1 ]
D'Agati, Vivette D. [2 ]
Lee, H. Thomas [1 ]
机构
[1] Columbia Univ, Coll Phys & Surg, Dept Anesthesiol, Anesthesiol Res Labs, New York, NY 10032 USA
[2] Columbia Univ, Coll Phys & Surg, Dept Pathol, New York, NY 10032 USA
基金
美国国家卫生研究院;
关键词
acute kidney injury; adenosine; apoptosis; inflammation; necrosis; transforming growth factor-beta 1; ACUTE KIDNEY INJURY; PROXIMAL TUBULE CELLS; ADENOSINE RECEPTORS PROTECT; MEDIATED TISSUE PROTECTION; SPHINGOSINE KINASE; HEPATIC ISCHEMIA; INTESTINAL EPITHELIA; TGF-BETA; MICE; ACTIVATION;
D O I
10.1038/ki.2013.43
中图分类号
R5 [内科学]; R69 [泌尿科学(泌尿生殖系疾病)];
学科分类号
1002 ; 100201 ;
摘要
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.
引用
收藏
页码:90 / 103
页数:14
相关论文
共 73 条
[1]  
[Anonymous], 2006, NATL HLTH STAT REPOR
[2]  
Aronson S, 1998, J CARDIOTHOR VASC AN, V17, P117
[3]   ATP drives lamina propria TH17 cell differentiation [J].
Atarashi, Koji ;
Nishimura, Junichi ;
Shima, Tatsuichiro ;
Umesaki, Yoshinori ;
Yamamoto, Masahiro ;
Onoue, Masaharu ;
Yagita, Hideo ;
Ishii, Naoto ;
Evans, Richard ;
Honda, Kenya ;
Takeda, Kiyoshi .
NATURE, 2008, 455 (7214) :808-U10
[4]   Adenosine Generation and Signaling during Acute Kidney Injury [J].
Bauerle, Jessica D. ;
Grenz, Almut ;
Kim, Jae-Hwan ;
Lee, H. Thomas ;
Eltzschig, Holger K. .
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY, 2011, 22 (01) :14-20
[5]   Cardioprotection by volatile anesthetics [J].
Bienengraeber, MW ;
Weihrauch, D ;
Kersten, JR ;
Pagel, PS ;
Warltier, DC .
VASCULAR PHARMACOLOGY, 2005, 42 (5-6) :243-252
[6]  
Bonventre JV, 2004, CONTRIB NEPHROL, V144, P19
[7]   Ischemic acute renal failure: An inflammatory disease? [J].
Bonventre, JV ;
Zuk, A .
KIDNEY INTERNATIONAL, 2004, 66 (02) :480-485
[8]   Recent advances in the pathophysiology of ischemic acute renal failure [J].
Bonventre, JV ;
Weinberg, JM .
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY, 2003, 14 (08) :2199-2210
[9]   Stat3 and Gfi-1 Transcription Factors Control Th17 Cell Immunosuppressive Activity via the Regulation of Ectonucleotidase Expression [J].
Chalmin, Fanny ;
Mignot, Gregoire ;
Bruchard, Melanie ;
Chevriaux, Angelique ;
Vegran, Frederique ;
Hichami, Aziz ;
Ladoire, Sylvain ;
Derangere, Valentin ;
Vincent, Julie ;
Masson, David ;
Robson, Simon C. ;
Eberl, Gerard ;
Pallandre, Jean Rene ;
Borg, Christophe ;
Ryffel, Bernhard ;
Apetoh, Lionel ;
Rebe, Cedric ;
Ghiringhelli, Francois .
IMMUNITY, 2012, 36 (03) :362-373
[10]   Mice that overexpress human heat shock protein 27 have increased renal injury following ischemia reperfusion [J].
Chen, Sean W. C. ;
Kim, Minjae ;
Kim, Mihwa ;
Song, Joseph H. ;
Park, Sang Won ;
Wells, Dominic ;
Brown, Kevin ;
de Belleroche, Jacqueline ;
D'Agati, Vivette D. ;
Lee, H. Thomas .
KIDNEY INTERNATIONAL, 2009, 75 (05) :499-510