The induction of macrophage hemeoxygenase-1 is protective during acute kidney injury in aging mice

被引：68

作者：

Ferenbach, David A. ^{[1
]}

Nkejabega, Noemie C. J. ^{[1
]}

McKay, Jennifer ^{[1
]}

Choudhary, Abhijeet K. ^{[1
]}

Vernon, Madeleine A. ^{[1
]}

Beesley, Matthew F. ^{[1
]}

Clay, Spike ^{[1
]}

Conway, Bryan C. ^{[1
]}

Marson, Lorna P. ^{[1
]}

Kluth, David C. ^{[1
]}

Hughes, Jeremy ^{[1
]}

机构：

[1] Univ Edinburgh, MRC Ctr Inflammat Res, Queens Med Res Inst, Edinburgh EH16 4TJ, Midlothian, Scotland

来源：

KIDNEY INTERNATIONAL | 2011年 / 79卷 / 09期

关键词：

aged; cell ablation; hemeoxygenase; ischemia-reperfusion; macrophages; ISCHEMIA-REPERFUSION INJURY; ACUTE-RENAL-FAILURE; HEME OXYGENASE-1 INDUCTION; ISCHEMIA/REPERFUSION INJURY; GENE-EXPRESSION; DENDRITIC CELLS; INFLAMMATION; PROTEIN; RATS; GLOMERULONEPHRITIS;

D O I：

10.1038/ki.2010.535

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：

100201 [内科学]; 100221 [泌尿外科学];

摘要：

Aging is thought to be associated with a higher susceptibility to renal ischemia-reperfusion injury (IRI). To study whether defective induction of hemeoxygenase-1 (HO-1, a protective and anti-inflammatory enzyme) might contribute to this, we found that while 12-month-old mice had similar baseline renal function and HO-1 expression, the induction of HO-1 usually seen in ischemia-reperfusion was reduced. This was also associated with worsened renal function and acute tubular necrosis in the aged compared with young mice. In the older mice, heme arginate (HA) induced HO-1 in the cortex and medulla, significantly improved renal function, and reduced tissue injury. Cellular HO-1 induction in the medulla in response to injury or HA treatment was found to be interstitial rather than epithelial, as evidenced by its colocalization with macrophage markers. In vitro, HA treatment of primary macrophages resulted in marked HO-1 induction without impairment of classical activation pathways. Macrophage depletion, caused by diphtheria toxin treatment of 12-month-old CD11b-DTR transgenic animals, resulted in the loss of interstitial HO-1-positive cells and reversal of the protective phenotype of HA treatment. Thus, failure of HO-1 induction following renal IRI worsens structural and functional injury in older mice and represents a therapeutic target in the elderly. Hence, HO-1-positive renal macrophages mediate HA-induced protection in IRI. Kidney International (2011) 79, 966-976; doi:10.1038/ki.2010.535; published online 19 January 2011

引用

页码：966 / 976

页数：11

共 44 条

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