转化生长因子-β1参与血小板诱导的内皮素-1生成刺激过程。

Involvement of transforming growth factor-beta 1 for platelets-induced stimulation of endothelin-1 production.

Matsumura Y, Murata S, Takada K, Takaoka M, Morimoto S

Department of Pharmacology, Osaka University of Pharmaceutical Sciences, Japan.

Clin Exp Pharmacol Physiol. 1994 Dec;21(12):991-6. doi: 10.1111/j.1440-1681.1994.tb02661.x.

Abstract

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.

摘要

研究了血小板刺激血管内皮细胞（EC）产生内皮素-1（ET-1）的可能机制。2. 血小板上清液刺激前内皮素原-1 mRNA的表达，随后培养的内皮细胞分泌的ET-1增加。用凝血酶预处理血小板可显著增强这些反应，该浓度的凝血酶不影响内皮细胞中ET-1的产生。通过可渗透的尼龙膜与培养的内皮细胞分离的血小板悬液也显著刺激内皮细胞分泌ET-1。3. 无论有无凝血酶预处理，血小板上清液增强的内皮素-1产生与上清液中活性转化生长因子-β1（TGF-β1）浓度相关。TGF-β1中和抗体可显著抑制上清液诱导的内皮细胞ET-1分泌增加。4. 我们初步得出结论，血小板通过释放一种生物活性可扩散物质（主要是TGF-β1）刺激内皮细胞产生ET-1。