Key result
Human urotensin II increased collagen-1 and decreased MMP-1 expression in HUVECs, an effect attenuated by MEK inhibition (P<0.01).
p-value: p=<0.01
Human urotensin II modulates collagen-1 and MMP-1 expression in human endothelial cells via MAPKp42/44 activation, suggesting a mechanistic role in vascular remodeling.
No immediate clinical implications; leaves open urotensin II's role in human vascular remodeling.
OBJECTIVES: Human urotensin II (hU-II) is a cyclic peptide highly expressed in cardiac tissues and blood vessels. hU-II is a potent vasoconstrictor. Recent studies indicate that urotensin II participates in myocardial remodeling after injury. This study was designed to study the role of hU-II in the expression of matrix metalloproteinase-1 (MMP-1) and collagen-1 in human umbilical vein endothelial cells (HUVECs) and underlying intracellular signaling mechanisms. METHODS AND RESULTS: Cultured HUVECs were incubated with hU-II (10 to 80 nM) for 3 to 24 hours. hU-II increased the expression (mRNA and protein) of collagen-1 in a concentration- and time-dependent manner. In contrast, hU-II decreased the expression and activity of MMP-1. Further, hU-II caused the phosphorylation of mitogen-activated protein kinase p42/44 (MAPKp42/44). This effect of hU-II was inhibited by pretreatment of cells with the MEK inhibitor (PD98059, 10 microM). In addition, treatment of cells with PD98059 attenuated protein expression of collagen-1 and MMP-1 elicited by hU-II (P < 0.01 versus hU-II alone). CONCLUSIONS: Our observations provide evidence that hU-II modulates the expression of MMP-1 and collagen-1 in HUVECs, and MAPKp42/44 activation may play a signal transduction role in this process.
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Wang et al. (2004) studied this question. Human urotensin II (hU-II) vs. hU-II alone vs hU-II + PD98059 was evaluated on Expression of MMP-1 and collagen-1 (p=<0.01). Human urotensin II increased collagen-1 and decreased MMP-1 expression in HUVECs, an effect attenuated by MEK inhibition (P<0.01).
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