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Signaling pathways of LIGHT induced macrophage migration and vascular smooth muscle cell proliferation
Author(s) -
Wei ChunYu,
Chou YinHsiang,
Ho FengMing,
Hsieh ShieLiang,
Lin WanWan
Publication year - 2006
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.20742
Subject(s) - microbiology and biotechnology , protein kinase b , vascular smooth muscle , mediator , signal transduction , phosphorylation , pi3k/akt/mtor pathway , macrophage , cell growth , receptor , kinase , chemistry , biology , endocrinology , smooth muscle , biochemistry , in vitro
The biological actions of LIGHT, a member of the tumor necrosis factor superfamily, are mediated by the interaction with lymphotoxin‐β receptor (LTβR) and/or herpes virus entry mediator (HVEM). Previous study demonstrated high‐level expressions of LIGHT and HVEM receptors in atherosclerotic plaques. To investigate the role of LIGHT in the functioning of macrophages and vascular smooth muscle cells (VSMC) in relation to atherogenesis, we determined the effects of LIGHT on macrophage migration and VSMC proliferation. We found LIGHT through HVEM activation can induce both events. LIGHT‐induced macrophage migration was associated with activation of signaling kinases, including MAPKs, PI3K/Akt, NF‐κB, Src members, and FAK. Proliferation of VSMC was also shown relating to the activation of MAPKs, PI3K/Akt, and NF‐κB, which consequently led to alter the expression of cell cycle regulatory molecules. Down‐regulation of p21, p27, and p53, and inversely up‐regulation of cyclin D and RB hyper‐phosphorylation were demonstrated. In conclusion, LIGHT acts as a novel mediator for macrophage migration and VSMC proliferation, suggesting its involvement in the atherogenesis. J. Cell. Physiol. 209: 735–743, 2006. © 2006 Wiley‐Liss, Inc.