ANP attenuates inflammatory signaling and Rho pathway of lung endothelial permeability induced by LPS and TNFalpha.
ANP attenuates inflammatory signaling and Rho pathway of lung endothelial permeability induced by LPS and TNFalpha.
复制标题
DOI：
10.1016/j.mvr.2009.11.006
复制
发表时间：
2010-01
影响因子：
3.1
通讯作者：
Birukova AA
中科院分区：
文献类型：
--
作者：
Xing J;Birukova AA
We have previously reported protective effects of atrial natriuretic peptide (ANP) against endothelial cell (EC) permeability induced by thrombin via suppression of Rho GTPase pathway of barrier dysfunction by protein kinase A and Epac-Rap1-Tiam1-Rac signaling cascades. This study tested effects of ANP on EC barrier dysfunction induced by inflammatory mediators lipopolysaccharide (LPS) and TNFα and linked them with activation of mitogen-activated protein kinase (MAPK) and NFκB signaling cascades known to promote EC hyperpermeability in the models of lung inflammation and sepsis. LPS and TNFα increased permeability in human pulmonary EC monitored by measurements of transendothelial electrical resistance, and caused disruption of EC monolayer integrity monitored by immunofluorescence staining for adherens junction marker protein VE-cadherin. Both disruptive effects were markedly attenuated by ANP. Both LPS and TNFα caused sustained activation of p38 and ERK1/2 MAP kinases, increased phosphorylation and degradation of negative regulator of NFκB signaling IkBα, and increased Rho-kinase mediated phosphorylation of myosin phosphatase MYPT1 leading to accumulation of phosphorylated myosin light chains. Consistent with protective effects on EC permeability and monolayer integrity, ANP dramatically attenuated activation of inflammatory signaling by LPS and TNFα in pulmonary EC. These results strongly suggest inhibitory effects of ANP on the LPS and TNFα induced inflammatory signaling as additional mechanism of EC barrier preservation in the models of acute lung injury and sepsis.
登录
查看更多内容
影响因子：
2.1
作者：
Lum, H;Malik, AB
通讯作者：
Malik, AB
影响因子：
4.5
作者：
Kim, Hee J.;Lee, Hui S.;Kang, Jihee Lee
通讯作者：
Kang, Jihee Lee
影响因子：
8.8
作者：
Reinhart, K;Karzai, W
通讯作者：
Karzai, W
影响因子：
4.8
作者：
Garcia, JGN;Wang, PY;Verin, AD
通讯作者：
Verin, AD
DOI：
10.1152/ajplung.00395.2006
发表时间：
2007-04-01
影响因子：
4.9
作者：
Birukova, Anna A.;Fu, Panfeng;Birukov, Konstantin G.
通讯作者：
Birukov, Konstantin G.