Signaling pathways of LIGHT induced macrophage migration and vascular smooth muscle cell proliferation.
The biological actions of LIGHT, a member of the tumor necrosis factor superfamily, are mediated by the interaction with lymphotoxin-beta receptor (LTbetaR) 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-kappaB, Src members, and FAK. Proliferation of VSMC was also shown relating to the activation of MAPKs, PI3K/Akt, and NF-kappaB, 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.
Wei
Chun-Yu
CY
Department of Pharmacology, College of Medicine, National Taiwan University, Taipei, Taiwan.
Chou
Yin-Hsiang
YH
Ho
Feng-Ming
FM
Hsieh
Shie-Liang
SL
Lin
Wan-Wan
WW
D000818:Animals; D050197:Atherosclerosis; D018797:Cell Cycle Proteins / Q000378:metabolism; D002465:Cell Movement / Q000502:physiology*; D049109:Cell Proliferation; D002478:Cells, Cultured; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000378:metabolism; D008264:Macrophages / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000166:cytology*; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000502:physiology*; D016328:NF-kappa B / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D053240:Receptors, Tumor Necrosis Factor, Member 14 / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D053326:Tumor Necrosis Factor Ligand Superfamily Member 14 / Q000235:genetics / Q000378:metabolism*; D019061:src-Family Kinases / Q000378:metabolism
D018797:Cell Cycle Proteins; D004791:Enzyme Inhibitors; D016328:NF-kappa B; D053240:Receptors, Tumor Necrosis Factor, Member 14; D053326:Tumor Necrosis Factor Ligand Superfamily Member 14; D019869:Phosphatidylinositol 3-Kinases; D019061:src-Family Kinases; D051057:Proto-Oncogene Proteins c-akt; D020928:Mitogen-Activated Protein Kinases