Endothelin-1 promotes mitogenesis in airway smooth muscle cells.
Endothelin-1 promotes mitogenesis in airway smooth muscle cells.
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Endothelin-1 促进气道平滑肌细胞有丝分裂。
DOI：
10.1165/ajrcmb.10.3.7509612
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发表时间：
1994
影响因子：
6.4
通讯作者：
Puett,D
中科院分区：
文献类型：
--
作者：
Glassberg,MK;Ergul,A;Wanner,A;Puett,D
内皮素以三种亚型（ET-1、ET-2 和 ET-3）存在，并在血管平滑肌中表现出血管收缩、支气管收缩和促进生长的特性。在气道中，ET-1 免疫反应性和 mRNA 已被检测到并定位于不同物种（包括人类）的上皮、平滑肌和内皮。有人提出，ET-1 可能在支气管哮喘患者气道平滑肌增生和肥大中发挥作用。我们在体外研究了绵羊气道平滑肌细胞 (SMC)，结果显示 [125I]ET-1 可饱和结合，解离常数 (Kd) 为 0.4 nM，ET-1 具有高亲和力结合位点 (Bmax)（104 fmol/10(6) 细胞）。这种结合是有效的，因为 ET-1 促进了这些肌肉细胞的有丝分裂，通过在没有血清的情况下细胞数量的增加来测量。将细胞暴露于从 1 pM 到 1 microM 分级剂量的 ET-1 后 24 小时，细胞数量以剂量依赖性方式显着超过对照。 ET-1 还使 c-fos mRNA 的瞬时表达比对照增强了 2.5 倍，最大表达发生在 30 分钟。这些观察结果提供了以下证据：(1)气道SMC具有ET-1的高亲和力结合位点，并且(2)根据细胞数量增加和c-fos mRNA表达的扩增确定，ET-1对气道SMC具有促有丝分裂作用。 ET-1 可能在影响气道平滑肌的生长方面发挥重要作用。
Endothelin exists as three isoforms (ET-1, ET-2, and ET-3) and exhibits vasoconstricting, bronchoconstricting, and growth-promoting properties in vascular smooth muscle. In the airways, ET-1 immunoreactivity and mRNA have been detected and localized to the epithelium, smooth muscle, and endothelium in different species, including humans. It has been suggested that ET-1 may have a role in the airway smooth muscle hyperplasia and hypertrophy seen in patients with bronchial asthma. We studied ovine airway smooth muscle cells (SMC) in vitro and showed saturable binding of [125I]ET-1 with a dissociation constant (Kd) of 0.4 nM and high affinity binding sites (Bmax) for ET-1 (104 fmol/10(6) cells). This binding was functional as ET-1 promoted mitogenesis of these muscle cells as measured by increased cell number in the absence of serum. Twenty-four hours after exposing the cells to graded doses of ET-1 from 1 pM to 1 microM, cell number increased significantly over control in a dose-dependent manner. ET-1 also enhanced the transient expression of c-fos mRNA by 2.5-fold over control, with maximal expression occurring at 30 min. These observations provide evidence that: (1) airway SMC possess high affinity binding sites for ET-1, and (2) ET-1 is mitogenic for airway SMC as determined by increased cell number and amplification of c-fos mRNA expression. ET-1 may have a fundamental role in influencing the growth of smooth muscle in the airways.