Open AccessTumor Necrosis Factor-α Inhibits Growth Factor–Mediated Cell Proliferation Through SHP-1 Activation in Endothelial Cells
Author(s) -
Hironori Nakagami,
Taixing Cui,
Masaru Iwai,
Tetsuya Shiuchi,
Yuko Takeda-Matsubara,
Lan Wu,
Masatsugu Horiuchi
Publication year - 2002
Publication title -
arteriosclerosis, thrombosis, and vascular biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.007
H-Index - 270
eISSN - 1524-4636
pISSN - 1079-5642
DOI - 10.1161/hq0202.104001
Subject(s) - epidermal growth factor , tumor necrosis factor alpha , vascular endothelial growth inhibitor , dephosphorylation , vascular endothelial growth factor , mapk/erk pathway , protein tyrosine phosphatase , biology , tyrosine phosphorylation , growth factor , endothelial stem cell , microbiology and biotechnology , vascular endothelial growth factor a , signal transduction , cell growth , growth factor receptor inhibitor , phosphorylation , cancer research , endocrinology , phosphatase , cell culture , biochemistry , growth factor receptor , in vitro , receptor , vegf receptors , genetics
Src homology 2–containing protein-tyrosine phosphatase 1 (SHP-1) is known to regulate signal transduction through the dephosphorylation of tyrosine kinases. In this study, we addressed the role of SHP-1 under tumor necrosis factor-α (TNF-α) stimulation in endothelial cells. The addition of recombinant vascular endothelial growth factor (50 ng/mL) or epidermal growth factor (50 ng/mL) significantly increased thymidine incorporation and c-fos promoter activity, whereas TNF-α (5 ng/mL) attenuated these effects in human or bovine aortic endothelial cells. In bovine aortic endothelial cells, we confirmed endogenous SHP-1 expression and that TNF-α activated SHP-1. Importantly, overexpression of dominant-negative SHP-1 attenuated the effect of TNF-α on thymidine incorporation and c-fos promoter activity. In addition, TNF-α attenuated vascular endothelial growth factor– and epidermal growth factor–induced extracellular signal–regulated kinase phosphorylation, whereas overexpression of dominant-negative SHP-1 prevented this inhibitory effect of TNF-α. Taken together, our results suggested that TNF-α inhibited growth factor–mediated cell proliferation through SHP-1 activation.