Effect of Notch activation on the regenerative response to acute renal failure
Effect of Notch activation on the regenerative response to acute renal failure
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DOI：
10.1152/ajprenal.00451.2009
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发表时间：
2010-01-01
影响因子：
4.2
通讯作者：
Rosenberg, Mark
中科院分区：
文献类型：
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作者：
Gupta, Sandeep;Li, Shunan;Rosenberg, Mark
[10]李伟，李伟. Notch激活对急性肾衰竭再生反应的影响。美国肾脏生理学杂志298：F209-F215，2010年。首次发表于2009年10月14日; doi：10.1152/ajprenal.00451.2009。急性肾功能衰竭（ARF）的发作并不总是完全可逆的，并可能导致慢性疾病，部分原因是再生反应不足。Notch信号通路参与决定发育过程中的细胞命运，以及成体器官中的组织维持和修复。本研究的目的是研究Notch通路在ARF后肾再生中的作用。缺血-再灌注诱导的肾损伤导致Notch通路的早期激活，如Notch 1和Notch 2细胞内结构域（切割的Notch）的表达增加所证明的。然后研究了Notch配体Delta-like-4（DLL 4）的外源性施用对从ARF恢复的影响。通过腹膜内注射DLL 4或媒介物对照对大鼠进行预处理。DLL 4末次给药后2天，通过双侧肾动脉夹闭45分钟，然后再灌注诱导ARF。DLL 4和对照组大鼠的肾损伤严重程度相似。DLL 4处理促进了肾恢复，如DLL 4处理的大鼠中血清肌酸酐在48小时内更快地恢复至基线所证明的，而在媒介物处理的对照大鼠中为5天。细胞增殖在DLL 4处理组中更高。总之，Notch通路的激活发生在ARF之后。用Notch配体DLL 4预处理增强了ARF的恢复，并代表了再生受损肾脏的潜在新治疗选择。
Gupta S, Li S, Abedin MJ, Wang L, Schneider E, Najafian B, Rosenberg M. Effect of Notch activation on the regenerative response to acute renal failure. Am J Physiol Renal Physiol 298: F209-F215, 2010. First published October 14, 2009; doi: 10.1152/ajprenal.00451.2009. Episodes of acute renal failure (ARF) are not always fully reversible and may lead to chronic disease, due in part to an inadequate regenerative response. The Notch signaling pathway is involved in determining cell fate during development, and tissue maintenance and repair in adult organs. The purpose of this study was to examine the role of the Notch pathway in renal regeneration following ARF. Kidney injury, induced by ischemia-reperfusion, resulted in early activation of the Notch pathway, as evidenced by increased expression of Notch1 and Notch2 intracellular domain (cleaved Notch). The effect of exogenous administration of the Notch ligand Delta-like-4 (DLL4) on recovery from ARF was then studied. Rats were pretreated by intraperitoneal injection of DLL4 or vehicle control. Two days following the last DLL4 dose, ARF was induced by bilateral renal artery clamping for 45 min followed by reperfusion. The severity of renal injury was similar in DLL4 and control rats. Renal recovery was facilitated by DLL4 treatment, as evidenced by faster return of serum creatinine to baseline by 48 h in DLL4-treated rats as against 5 days in vehicle-treated control rats. Cell proliferation was higher in the DLL4-treated group. In conclusion, activation of the Notch pathway occurs following ARF. Pretreatment with the Notch ligand DLL4 enhanced recovery from ARF and represents a potential novel therapeutic option for regenerating the injured kidney.