Activation of Parenchymal CD47 Promotes Renal Ischemia-Reperfusion Injury

被引:61
作者
Rogers, Natasha M. [1 ,2 ]
Thomson, Angus W. [2 ]
Isenberg, Jeffrey S. [1 ]
机构
[1] Univ Pittsburgh, Sch Med, Vasc Med Inst, Div Pulm Allergy & Crit Care Med, Pittsburgh, PA 15261 USA
[2] Univ Pittsburgh, Sch Med, Starzl Transplantat Inst, Pittsburgh, PA 15261 USA
来源
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY | 2012年 / 23卷 / 09期
基金
美国国家卫生研究院; 英国医学研究理事会;
关键词
DELAYED GRAFT FUNCTION; NITRIC-OXIDE; CELL RESPONSES; KIDNEY; APOPTOSIS; SURVIVAL; TISSUE; TRANSPLANTATION; INHIBITION; INDUCTION;
D O I
10.1681/ASN.2012020137
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
Ischemia-reperfusion injury (IRI) contributes to decreased allograft function and allograft rejection in transplanted kidneys. Thrombospondin-1 is a stress protein typically secreted in response to hypoxia and the ligand activator for the ubiquitously expressed receptor CD47. The function of activated CD47 in IRI remains completely unknown. Here, we found that both CD47 and its ligand thrombospondin-1 were upregulated after renal IRI in mice. CD47-knockout mice were protected against renal dysfunction and tubular damage, suggesting that the development of I RI requires intact CD47 signaling. Chimeric CD47-knockout mice engrafted with wild-type hematopoietic cells had significantly lower serum creatinine and less tubular damage than wild-type controls after IRI, suggesting that CD47 signaling in parenchymal cells predominantly mediates renal damage. Treatment with a CD47-blocking antibody protected mice from renal dysfunction and tubular damage compared with an isotype control. Taken together, these data imply that CD47 on parenchymal cells promotes injury after renal ischemia and reperfusion. Therefore, CD47 blockade may have therapeutic potential to prevent or suppress ischemia-reperfusion-mediated damage.
引用
收藏
页码:1538 / 1550
页数:13
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