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首页> 外文期刊>American Journal of Physiology >Estrogen-induced proliferation of urothelial cells is modulated by nerve growth factor.
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Estrogen-induced proliferation of urothelial cells is modulated by nerve growth factor.

机译:雌激素诱导的尿路上皮细胞增殖受神经生长因子调节。

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Both nerve growth factor (NGF) and estrogen have been shown to stimulate proliferation of various cell types. Human urothelial cells (HUC) express the alpha- and beta-subtypes of the estrogen receptor (ER(alpha) and ER(beta)) as well as tyrosine kinase A (trkA), the high-affinity receptor for NGF. We investigated interactions between estrogen and NGF relative to cell proliferation using primary cultures of HUC. 17 beta-estradiol (E2) stimulated NGF synthesis by HUC, and E2 (50 nM), the ER(alpha) agonist 16 alpha-iodo-17 beta-estradiol (10 nM), or the ER(beta) agonist genistein (50 nM) each stimulated HUC proliferation, an effect that was abolished by the estrogen antagonist ICI-182,780 (100 nM). NGF (1-100 ng/ml) stimulated HUC proliferation, and this was abolished by NGF antiserum (0.1 microl/ml) or the trkA antagonist K252a (100 nM). HUC proliferation stimulated by E2 was also abolished by NGF antiserum or K252a. Finally, we observed that treatment of HUC with NGF (50 ng/ml) or E2 (50 nM) stimulated trkA phosphorylation, and this was abolished by K252a (100 nM) or NGF antiserum (0.1 microl/ml). These data indicate that the effects of ER activation on HUC proliferation at least partly involve activation of trkA by NGF.
机译:神经生长因子(NGF)和雌激素均已显示出可刺激各种细胞类型的增殖。人尿道上皮细胞(HUC)表达雌激素受体(ERα和ERβ)以及酪氨酸激酶A(trkA)(NGF的高亲和力受体)的α和β亚型。我们使用HUC的原代培养研究了雌激素和NGF之间相对于细胞增殖的相互作用。 17β-雌二醇(E2)通过HUC刺激NGF的合成,以及E2(50 nM),ERα激动剂16 alpha-iodo-17β-雌二醇(10 nM)或ERβ激动剂染料木黄酮(50 nM)各自刺激HUC增殖,雌激素拮抗剂ICI-182,780(100 nM)取消了这一作用。 NGF(1-100 ng / ml)刺激了HUC增殖,被NGF抗血清(0.1 microl / ml)或trkA拮抗剂K252a(100 nM)废除了。 NGF抗血清或K252a也消除了E2刺激的HUC增殖。最后,我们观察到用NGF(50 ng / ml)或E2(50 nM)处理HUC会刺激trkA磷酸化,而K252a(100 nM)或NGF抗血清(0.1 microl / ml)则消除了磷酸化。这些数据表明ER激活对HUC增殖的影响至少部分涉及NGF对trkA的激活。

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