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首页> 外文期刊>Journal of Cellular Physiology >Induction of autocrine epidermal growth factor receptor ligands in human keratinocytes by insulin/insulin-like growth factor-1.
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Induction of autocrine epidermal growth factor receptor ligands in human keratinocytes by insulin/insulin-like growth factor-1.

机译:诱导自分泌表皮生长因子受体配体在人类角质细胞胰岛素/胰岛素样生长因子- 1。

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摘要

Autocrine activation of the epidermal growth factor (EGF) receptor on keratinocytes has been recognized as an important growth regulatory mechanism involved in epithelial homeostasis, and, possibly, hyperproliferative diseases. Insulin-like growth factor (IGF)-1 and insulin have been shown to be paracrine keratinocyte mitogens that bind to the type I IGF receptor which is expressed on actively proliferating keratinocytes in situ. In this report, we demonstrate that IGF-1/insulin induced production of keratinocyte-derived autocrine growth factors that bind to the EGF receptor. Increased steady-state mRNA levels for transforming growth factor alpha (TGF-alpha) and for amphiregulin (AR) were observed upon incubation of keratinocytes with mitogenic concentrations of IGF-1. IGF-1 also induced production and secretion of TGF-alpha and AR proteins as detected by immunoassays. An EGF receptor antagonistic monoclonal antibody abolished the mitogenic effect of IGF-1 on cultured keratinocytes. These results suggest that stimulation of keratinocyte growth of IGF-1 requires activation of an EGF receptor-mediated autocrine loop.
机译:自分泌表皮生长的激活在角化细胞因子(EGF)受体被认为是一个重要的增长的监管参与上皮内稳态机制,可能,hyperproliferative疾病。胰岛素样生长因子(IGF 1)和胰岛素旁分泌角化细胞已被证明吗有丝分裂原绑定到类型我IGF受体表示在积极激增角化细胞原位。证明igf - 1 /胰岛素诱导生产的keratinocyte-derived自分泌生长因子表皮生长因子受体结合。稳态mRNA水平将增长系数α(是)和amphiregulin(AR)是观察在孵化角化细胞的促有丝分裂的浓度igf - 1。是基于“增大化现实”技术的蛋白质的分泌检测到免疫测定。对立的单克隆抗体废除了促有丝分裂的igf - 1对培养的影响角化细胞。刺激的角化细胞igf - 1的增长需要激活EGF受体介导的自分泌循环。

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