期刊
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY
卷 306, 期 6, 页码 H789-H796出版社
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpheart.00559.2013
关键词
myofibroblasts; VEGF-C; collagen synthesis; collagen degradation; TGF-beta 1; ERK
资金
- National Heart, Lung, and Blood Institute [1RO1-HL-096503]
Vascular endothelial growth factor (VEGF)-C is a key mediator of lymphangiogenesis. Our recent study shows that VEGF-C/VEGF receptors (VEGFR)-3 are significantly increased in the infarcted rat myocardium, where VEGFR-3 is expressed not only in lymph ducts but also in myofibroblasts, indicating that VEGF-C has an unrevealed role in fibrogenesis during cardiac repair. The current study is to explore the regulation and molecular mechanisms of VEGF-C in fibrogenesis. The potential regulation of VEGF-C on myofibroblast differentiation/growth/migration, collagen degradation/synthesis, and transforming growth factor (TGF)-beta and ERK pathways was detected in cultured cardiac myofibroblasts. Our results showed that VEGF-C significantly increased myofibroblast proliferation, migration, and type I/III collagen production. Matrix metalloproteinase (MMP)-2 and -9 were significantly elevated in the medium of VEGF-C-treated cells, coincident with increased tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2. Furthermore, VEGF-C activated the TGF-beta 1 pathway and ERK phosphorylation, which was significantly suppressed by TGF-beta or ERK blockade. This is the first study indicating that in addition to lymphangiogenesis, VEGF-C is also involved in fibrogenesis through stimulation of myofibroblast proliferation, migration, and collagen synthesis, via activation of the TGF-beta 1 and ERK pathways.
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