Human urotensin II modulates collagen synthesis and the expression of MMP-1 in human endothelial cells.
OBJECTIVE
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.


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.
Wang
Hong
H
Renhe Hospital, Shanghai, China.
Mehta
Jawahar L
JL
Chen
Kui
K
Zhang
Xingjiang
X
Li
Dayuan
D
D002478:Cells, Cultured; D024042:Collagen Type I / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects; D042783:Endothelial Cells / Q000187:drug effects* / Q000502:physiology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D005419:Flavonoids / Q000494:pharmacology; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology; D020781:Matrix Metalloproteinase 1 / Q000096:biosynthesis / Q000235:genetics; D061965:Matrix Metalloproteinase Inhibitors; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D010766:Phosphorylation; D013997:Time Factors; D014471:Umbilical Veins / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D015854:Up-Regulation / Q000187:drug effects* / Q000235:genetics; D014579:Urotensins / Q000235:genetics / Q000494:pharmacology*
D024042:Collagen Type I; D005419:Flavonoids; D061965:Matrix Metalloproteinase Inhibitors; D014579:Urotensins; C029677:urotensin II; D019950:Mitogen-Activated Protein Kinase 1; D020781:Matrix Metalloproteinase 1; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one