Stretch activates heparin-binding EGF-like growth factor expression in bladder smooth muscle cells
Stretch activates heparin-binding EGF-like growth factor expression in bladder smooth muscle cells
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DOI：
10.1152/ajpcell.1998.275.5.c1247
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发表时间：
1998-11-01
影响因子：
5.5
通讯作者：
Peters, CA
中科院分区：
文献类型：
--
作者：
Park, JM;Borer, JG;Peters, CA
培养的大鼠膀胱平滑肌细胞（SMC）生长在胶原蛋白涂层的硅胶膜，并进行连续周期的拉伸松弛。半定量RT-PCR分析显示，肝素结合表皮生长因子（EGF）样生长因子（KB-EGF）mRNA水平的增加后，拉伸时间依赖性，最高水平出现后4小时。免疫组化显示HB-EGF蛋白在拉伸比在nonstretched SMC更高的水平。血管紧张素Ⅱ受体1型拮抗剂氯沙坦显着抑制牵张激活HB-EGF的表达。ANG II水平在拉伸中比在非拉伸条件培养基中高3.3倍。膀胱平滑肌细胞的拉伸刺激，已瞬时转染HB-EGF启动子荧光素酶表达构建体导致报告活性增加11倍。机械拉伸诱导的氚化胸苷掺入率增加4.7倍，这是减少了25%，在氯沙坦的存在下。我们得出结论，机械拉伸激活HB-EGF基因表达在膀胱平滑肌细胞，这是介导的自分泌ANG II分泌的一部分。
Cultured rat bladder smooth muscle cells (SMC) were grown on collagen-coated silicone membranes and subjected to continuous cycles of stretch-relaxation. Semiquantitative RT-PCR analysis revealed a time-dependent increase in heparin-binding epidermal growth factor (EGF)-like growth factor (KB-EGF) mRNA levels after stretch, with maximal levels appearing after 4 h. Immunostaining for proHB-EGF revealed higher levels of HB-EGF protein in the stretched than in the nonstretched SMC. The ANG II receptor type 1 antagonist losartan markedly suppressed stretch-activated HB-EGF expression. ANG II levels were 3.3-fold higher in the stretch- than in the non-stretch-conditioned media. Stretch stimulation of bladder SMC that had been transiently transfected with an HB-EGF promoter-luciferase expression construct resulted in an 11-fold increase in reporter activity. Mechanical stretch induced a 4.7-fold increase in tritiated thymidine incorporation rate, and this was reduced by 25% in the presence of losartan. We conclude that mechanical stretch activates HB-EGF gene expression in bladder SMC and that this is mediated in part by autocrine ANG II secretion.