title: Caveolin-1 regulates Rac1 activation and rat pulmonary microvascular endothelial hyperpermeability induced by TNF-α.
abstract: 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-α-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-α 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-α.
authors: Department of Respiratory Medicine, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, People's Republic of China.
authors: Min
authors: M
authors: Shao
authors: Yang
authors: Y
authors: Yue
authors: Geng-Yun
authors: GY
authors: Sun
authors: Qing-Hai
authors: QH
authors: You
authors: Nan
authors: N
authors: Wang
authors: Dan
authors: D
authors: Zhang
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002199:Capillary Permeability / Q000502:physiology*; D051242:Caveolin 1 / Q000378:metabolism*; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000378:metabolism; D042783:Endothelial Cells / Q000378:metabolism; D016650:Fluorescein-5-isothiocyanate; D005455:Fluorescent Antibody Technique; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D015151:Immunoblotting; D008168:Lung / Q000098:blood supply*; D008856:Microscopy, Fluorescence; D034741:RNA, Small Interfering / Q000235:genetics; D051381:Rats; D014162:Transfection / Q000379:methods; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D020830:rac1 GTP-Binding Protein / Q000378:metabolism*
chemical_list: D051242:Caveolin 1; D018076:DNA, Complementary; D034741:RNA, Small Interfering; D014409:Tumor Necrosis Factor-alpha; C499134:Rac1 protein, rat; D020830:rac1 GTP-Binding Protein; D016650:Fluorescein-5-isothiocyanate
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