A novel mechanism of NALP3 inducing ischemia reperfusion injury by activating MAPK pathway in acute renal failure
A novel mechanism of NALP3 inducing ischemia reperfusion injury by activating MAPK pathway in acute renal failure
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DOI：
10.1016/j.mehy.2012.12.041
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发表时间：
2013-04-01
影响因子：
4.7
通讯作者：
Li, R. S.
中科院分区：
文献类型：
--
作者：
Hao, J. L.;Li, Y. F.;Li, R. S.
急性肾功能衰竭（ARF）是一种肾功能的快速丧失。迄今为止，这种情况发生的原因和机制尚不清楚，因此对这种疾病的管理造成了障碍。目前，以公认的肾缺血再灌注损伤（I/R injury，I/R injury）模型为代表的ARF的实验研究主要集中在几个可能的相关因素，如活性氧、无复流现象、细胞凋亡和广泛的炎症反应。后者目前被谈论得很多。一些细胞内危险感测蛋白，如称为NLR的含核苷酸结合结构域亮氨酸重复序列的家族蛋白，通过形成称为炎性体的多蛋白复合物来调节炎症反应。该复合物的最经典的家族成员是NALP3，其被证实是I/R损伤的贡献者。然而，它如何有助于病理仍然不清楚。广泛的炎症反应被认为是由丝裂原活化蛋白激酶（MAPK）信号通路调节。NLR的另一个家族成员NOD2与NALP3有着相似的结构，它能诱导MAPK信号通路的激活，因此我们推测NALP3可能通过激活MAPK信号通路参与了缺血再灌注损伤的过程。如果这一假设被证明是正确的，它可能有利于ARF的管理。(C)2013爱思唯尔有限公司保留所有权利。
Acute renal failure (ARF) is a rapid loss of kidney function. The reasons and mechanism by which this occurs has not been clarified so far thus creating obstacles to management of this disease. Presently, the experimental research using the accepted renal ischemia reperfusion injury (I/R injury) model represented for ARF focuses on several possible relevant factors such as reactive oxygen species, no-reflow phenomenon, apoptosis and extensive inflammatory response. The latter is much talked about currently. Some intracellular danger sensing proteins, such as the nucleotide binding domain leucine rich repeats-containing family proteins known as NLRs, adjust the inflammatory response through the formation of a multi-protein complex known as an inflammasome. The most classic family member of this complex is NALP3 confirmed to serve as a contributor to I/R injury. However, how it contributes to the pathology remains obscure. The extensive inflammatory response is considered to be modulated by the mitogen-activated protein kinases (MAPK) signaling pathway. NOD2, another family member of NLR, which shares similar structure with NALP3, indicated that it induced the activation of MAPK in response to a pathogen, thus we assumed that NALP3 performed the harmful process of I/R injury, resulting probably from the activation of the MAPK signaling pathway. If this hypothesis proves to be correct, it might benefit the management of ARF. (C) 2013 Elsevier Ltd. All rights reserved.