Caveolin-1 Regulates Rac1 Activation and Rat Pulmonary Microvascular Endothelial Hyperpermeability Induced by TNF-α

被引：15

作者：

Shao, Min ^{[1
,2
]}

Yue, Yang ^{[1
]}

Sun, Geng-Yun ^{[1
]}

You, Qing-Hai ^{[1
]}

Wang, Nan ^{[1
]}

Zhang, Dan ^{[1
]}

机构：

[1] Anhui Med Univ, Affiliated Hosp 1, Dept Resp Med, Hefei, Anhui, Peoples R China

[2] Anhui Med Univ, Dept Crit Care Med, Anhui Prov Hosp, Hefei, Anhui, Peoples R China

来源：

PLOS ONE | 2013年 / 8卷 / 01期

基金：

中国国家自然科学基金;

关键词：

NF-KAPPA-B; RHO-GTPASES; INTRACELLULAR CA2+; CELL POLARIZATION; BARRIER INTEGRITY; REACTIVE OXYGEN; SMOOTH-MUSCLE; NITRIC-OXIDE; PERMEABILITY; KINASE;

D O I：

10.1371/journal.pone.0055213

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

A multiplicity of vital cellular and tissue level functions are controlled by caveolin-1 and it is considered to be an important candidate for targeted therapeutics. Rac1-cortactin signaling plays an important role in maintaining the functions of the endothelial barrier in microvascular endothelial cells. The activity of Rac1 has been shown to be regulated by caveolin-1. Therefore, the present study investigated the consequences of down-regulating caveolin-1 and the subsequent changes in activity of Rac1 and the endothelial barrier functions in primary rat pulmonary microvascular endothelial cells (RPMVECs). RPMVECs were transfected with a small hairpin RNA duplex to down-regulate caveolin-1 expression. This procedure significantly increased the activity of Rac1. Moreover, down-regulation of caveolin-1 attenuated TNF-alpha-induced decrease in TER, increase in the flux of FITC-BSA and the disappearance of cortactin from the cell periphery in RPMVEC. Rac1 inhibitors significantly abolished this barrier-protective effect induced by down-regulation of caveolin-1 in response to TNF-alpha in RPMVECs. In conclusion, our data suggest a mechanism for the regulation of Rac1 activity by caveolin-1, with consequences for activation of endothelial cells in response to TNF-alpha.

引用

页数：12

共 60 条

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