Involvement of transforming growth factor-beta 1 for platelets-induced stimulation of endothelin-1 production.
1. Possible mechanisms by which platelets stimulate the production of endothelin-1 (ET-1) in vascular endothelial cells (EC) were investigated. 2. A supernatant of platelets stimulated the expression of prepro ET-1 mRNA, followed by an increased secretion of ET-1 from cultured EC. These responses were markedly enhanced by pretreatment of the platelets with thrombin, at a concentration which did not influence the ET-1 production in EC. A platelet suspension, separated from cultured EC by a permeable nylon membrane, also markedly stimulated the ET-1 secretion from EC. 3. Endothelin-1 production enhanced by the platelet supernatant, with or without thrombin pretreatment, correlated with the active transforming growth factor-beta 1 (TGF-beta 1) concentrations in the supernatant. The supernatant-induced increase in ET-1 secretion from the EC was markedly suppressed by TGF-beta 1 neutralizing antibody. 4. We tentatively conclude that platelets stimulate the endothelial ET-1 production by releasing a bioactive diffusible substance, mainly TGF-beta 1.
Matsumura
Y
Y
Department of Pharmacology, Osaka University of Pharmaceutical Sciences, Japan.
Murata
S
S
Takada
K
K
Takaoka
M
M
Morimoto
S
S
D000818:Animals; D001792:Blood Platelets / Q000502:physiology*; D015152:Blotting, Northern; D002417:Cattle; D002478:Cells, Cultured; D019332:Endothelin-1; D016232:Endothelins / Q000096:biosynthesis*; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D007124:Immunoenzyme Techniques; D011498:Protein Precursors / Q000096:biosynthesis; D012333:RNA, Messenger / Q000096:biosynthesis; D011863:Radioimmunoassay; D051381:Rats; D013552:Swine; D016212:Transforming Growth Factor beta / Q000494:pharmacology / Q000502:physiology*
D019332:Endothelin-1; D016232:Endothelins; D011498:Protein Precursors; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta