PGE(2) stimulates vascular smooth muscle cell proliferation via the EP2 receptor.
Prostaglandins released by injured vascular tissue can modulate smooth muscle cell (SMC) proliferation. The mechanism of action of PGE(2) was investigated with porcine coronary artery SMCs obtained by explant culture. DNA and RNA syntheses exhibited a concentration-dependent increase following treatment of quiescent SMCs with PGE(2), while PGI(2) had no effect. PGE(2) also elevated PCNA expression, bromodeoxyuridine incorporation, and cell number, indicative of a hyperplastic growth response. Furthermore, induction of c-fos expression required activation of both phosphatidylinositol 3-kinase and mitogen-activated protein kinase. Contrary to these data, treatment of proliferating cells with PGE(2) caused a reduction in DNA synthesis. A role for PKA in either growth stimulation or inhibition was excluded. Interestingly, only quiescent SMCs expressed EP2 receptors, and the selective EP2 receptor agonist butaprost confirmed that this receptor was essential for growth stimulation and possibly inhibition. These data suggest that the growth state-dependent actions of PGE(2) on SMC proliferation may be mediated via the EP2 receptor.
Yau
Lorraine
L
Department of Physiology, University of Manitoba, Manitoba, Canada.
Zahradka
Peter
P
D000818:Animals; D002455:Cell Division; D003331:Coronary Vessels; D000242:Cyclic AMP / Q000502:physiology; D004247:DNA / Q000096:biosynthesis; D015232:Dinoprostone / Q000502:physiology*; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000166:cytology*; D032389:Myocytes, Smooth Muscle / Q000166:cytology*; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D018078:Receptors, Prostaglandin E / Q000502:physiology*; D058307:Receptors, Prostaglandin E, EP2 Subtype; D013552:Swine
D016760:Proto-Oncogene Proteins c-fos; D018078:Receptors, Prostaglandin E; D058307:Receptors, Prostaglandin E, EP2 Subtype; D004247:DNA; D000242:Cyclic AMP; D019869:Phosphatidylinositol 3-Kinases; D019950:Mitogen-Activated Protein Kinase 1; D015232:Dinoprostone