Regulated expression of endothelin 1 in glomerular capillary endothelial cells.
Regulated expression of endothelin 1 in glomerular capillary endothelial cells.
复制标题
调节肾小球毛细血管内皮细胞中内皮素 1 的表达。
DOI：
10.1152/ajprenal.1991.261.1.f117
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发表时间：
1991
期刊：
影响因子：
--
通讯作者：
Ballermann,BJ
中科院分区：
文献类型：
--
作者：
Marsden,PA;Dorfman,DM;Collins,T;Brenner,BM;Orkin,SH;Ballermann,BJ
内皮素（ET）-1是一种强有力的血管收缩剂，已知由内衬大血管的内皮细胞产生和分泌。由于ET-1刺激肾小球系膜细胞收缩，肾小球毛细血管内皮细胞（GEN），通常位于密切贴壁肾小球系膜细胞，检查潜在的ET表达和分泌。培养牛GEN释放ET的时间依赖性的方式。ET分泌显着刺激缓激肽，一种激动剂，已知激活磷脂酶C在这些细胞。前内皮素原1（preproET-1）mRNA水平在GEN上升，在双相的方式与缓激肽刺激。早期增量（在30分钟）不依赖于新的蛋白质合成，而后期上升（6小时后，除了缓激肽）似乎是蛋白质合成依赖。无论是早期还是晚期缓激肽刺激肾小球内皮细胞preproET-1 mRNA的表达是由于抑制mRNA的分解。两个阶段的preproET-1 mRNA的表达与其他肾小球内皮细胞钙动员激动剂，即凝血酶，并模仿钙离子载体离子霉素。相比之下，蛋白激酶C激活剂佛波醇肉豆蔻酸酯乙酸酯仅在30分钟时增强preproET-1 mRNA表达，此后抑制表达。结论：GEN具有以磷脂酶C调节的方式表达和分泌ET-1的潜力。此外，由于肾小球系膜细胞对这种肽有反应，研究结果提高了肾小球内皮细胞衍生的ET-1对系膜细胞张力的旁分泌调节的可能性。
Endothelin (ET)-1 is a powerful vasoconstrictor known to be produced and secreted by endothelial cells lining large vessels. Because ET-1 stimulates glomerular mesangial cell contraction, glomerular capillary endothelial cells (GEN), normally situated in close apposition to mesangial cells, were examined for potential ET expression and secretion. Cultured bovine GEN released ET in a time-dependent fashion. ET secretion was significantly stimulated by bradykinin, an agonist known to activate phospholipase C in these cells. Preproendothelin 1 (preproET-1) mRNA levels in GEN rose in a biphasic manner on stimulation with bradykinin. The early increments (at 30 min) were not dependent on new protein synthesis, whereas the late rise (6 h after addition of bradykinin) appeared to be protein synthesis dependent. Neither early or late bradykinin-stimulated preproET-1 mRNA expression in glomerular endothelial cells was due to inhibition of mRNA breakdown. Both phases of preproET-1 mRNA expression were observed with other glomerular endothelial cell calcium-mobilizing agonists, namely thrombin, and were mimicked by the calcium ionophore ionomycin. By contrast, the protein kinase C activator phorbol myristate acetate only enhanced preproET-1 mRNA expression at 30 min and suppressed expression thereafter. It is concluded that GEN have the potential to express and secrete ET-1 in a phospholipase C-regulated fashion. Furthermore, because glomerular mesangial cells respond to this peptide, the findings raise the possibility of paracrine regulation of mesangial cell tone by glomerular endothelial cell-derived ET-1.