Morg1 heterozygous mice are protected from acute renal ischemia-reperfusion injury
Morg1 heterozygous mice are protected from acute renal ischemia-reperfusion injury
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DOI：
10.1152/ajprenal.00204.2009
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发表时间：
2009-11-01
影响因子：
4.2
通讯作者：
Wolf, Gunter
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文献类型：
--
作者：
Hammerschmidt, Elke;Loeffler, Ivone;Wolf, Gunter
放大图片作者：Hammerschampe，Loeffler I，Wolf G. Morg 1杂合子小鼠免受急性肾缺血-再灌注损伤。美国肾脏生理学杂志297：F1273-F1287，2009年。首次发表于2009年9月2日; doi：10.1152/ajprenal.00204.2009.-当肾脏中的促炎和凋亡过程被激活时，肾缺血和再灌注损伤导致急性肾衰竭。缺氧诱导转录因子-α（HIF-α）是一种重要的基因转录因子，其表达增加可减轻缺血性肾损伤。我们最近发现了一种新的WD重复蛋白Morg 1（MAPK组织者1），它与脯氨酰羟化酶3（PHD 3）相互作用，PHD 3是一种参与HIF-1 α和HIF-2 α表达调控的重要酶。虽然纯合子Morg 1-/-小鼠是胚胎致死的，但杂合子Morg 1 +/-小鼠具有正常的表型。我们在这里表明，Morg 1 +/-部分保护肾缺血再灌注损伤相比，野生型Morg 1 +/+动物。Morg 1 +/-小鼠与野生型动物相比，缺血再灌注肾中HIF-1 α和HIF-2 α表达的增加更强，与血清促红细胞生成素水平升高相关。然而，在非缺血性肾脏中没有发现HIF-1 α和HIF-2 α的显著表达，在Morg 1 +/-和Morg 1 +/+小鼠之间没有任何差异。Morg 1 +/-小鼠的缺血肾脏比野生型动物的缺血肾脏表达更多的促红细胞生成素mRNA。与野生型小鼠相比，Morg 1 +/-小鼠的肾缺血导致肾脏炎症减少和促炎细胞因子（MCP-1，IP-10，MIP-2）减少。此外，缺血再灌注后Morg 1 +/-肾脏的细胞凋亡和肾小管损伤显著减少，这也反映在与野生型相比肾功能显著改善。因此，Morg 1可能是一个新的治疗靶点，以限制缺血再灌注后的肾损伤。
Hammerschmidt E, Loeffler I, Wolf G. Morg1 heterozygous mice are protected from acute renal ischemia-reperfusion injury. Am J Physiol Renal Physiol 297: F1273-F1287, 2009. First published September 2, 2009; doi: 10.1152/ajprenal.00204.2009.-Renal ischemia and reperfusion injury leads to acute renal failure when proinflammatory and apoptotic processes in the kidney are activated. The increase in hypoxia-inducible transcription factor-alpha (HIF-alpha), an important transcription factor for several genes, can attenuate ischemic renal injury. We recently identified a novel WD-repeat protein designated Morg1 (MAPK organizer 1) that interacts with prolyl hydroxylase 3 (PHD3), an important enzyme involved in the regulation of HIF-1 alpha and HIF-2 alpha expression. While homozygous Morg1 -/- mice are embryonic lethal, heterozygous Morg1 +/- mice have a normal phenotype. We show here that Morg1 +/- were partially protected from renal ischemia-reperfusion injury compared with wild-type Morg1 +/+ animals. Morg1 +/- mice compared with wild-type animals revealed a stronger increase in HIF-1 alpha and HIF-2 alpha expression in the ischemic-reperfused kidney associated with enhanced serum erythropoietin levels. However, no significant expression of HIF-1 alpha and HIF-2 alpha was found in nonischemic kidneys without any difference between Morg1 +/- and Morg1 +/+ mice. Ischemic kidneys of Morg1 +/- mice expressed more erythropoietin mRNA than ischemic kidneys from wild-type animals. Renal ischemia in Morg1 +/- mice resulted in a decrease in renal inflammation and reduction of proinflammatory cytokines (MCP-1, IP-10, MIP-2) compared with wild-type mice. Furthermore, there was significantly less apoptosis and tubular damage in Morg1 +/- kidneys after ischemia-reperfusion, and this was also reflected in significantly improved renal function compared with wild-type. Thus Morg1 may be a novel therapeutic target to limit renal injury after ischemia-reperfusion.