Production of endothelin-1 in vascular endothelial cells is regulated by factors associated with vascular injury.
We studied the effects of factors associated with vascular injury on the production of endothelin-1 (ET-1) in cultured porcine aortic endothelial cells. ET-1 mRNA expression and peptide production in endothelial cells were increased by thrombin, transforming growth factor beta 1 (TGF beta 1), interleukin-1 (IL-1) and tumor necrotizing factor alpha (TNF alpha). The analysis of the enhancer/promoter region of the human ET-1 gene showed that the ET-1 gene transcription is regulated in a cell-specific manner and is activated by thrombin, TGF beta 1 and IL-1. These results suggest that the production of ET-1 in endothelial cells is regulated by factors associated with platelet aggregation, macrophage infiltration and the formation of atherosclerotic lesions.
Maemura
K
K
Third Department of Internal Medicine, Faculty of Medicine, University of Tokyo, Japan.
Kurihara
H
H
Morita
T
T
Oh-hashi
Y
Y
Yazaki
Y
Y
D000818:Animals; D001161:Arteriosclerosis / Q000209:etiology / Q000378:metabolism; D002478:Cells, Cultured; D016232:Endothelins / Q000096:biosynthesis* / Q000235:genetics; D004730:Endothelium, Vascular / Q000187:drug effects / Q000293:injuries / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D007375:Interleukin-1 / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013552:Swine; D013917:Thrombin / Q000494:pharmacology; D014158:Transcription, Genetic / Q000187:drug effects; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D016232:Endothelins; D007375:Interleukin-1; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D013917:Thrombin