Spatial and temporal patterns of expression of epidermal growth factor, transforming growth factor alpha and transforming growth factor beta 1-3 and their receptors in mouse jejunum after radiation treatment

Spatial and temporal patterns of expression of epidermal growth factor, transforming growth factor alpha and transforming growth factor beta 1-3 and their receptors in mouse jejunum after radiation treatment
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DOI:
10.2307/3579436
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发表时间:
1997-01-01
期刊:
影响因子:
3.4
通讯作者:
Thames, HD
Thames, HD
中科院分区:
医学3区
文献类型:
--
作者:
Ruifrok, ACC;Mason, KA;Thames, HD

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本研究的目的是评估照射后小鼠空肠增殖的变化以及生长因子EGF、TGF-α和TGF-β(1-3)在增殖反应中的作用。我们的工作假设是,从绒毛到隐窝中细胞的反馈信号调节增殖,并且生长因子EGF和TGF-α及其共同受体EGF-R参与刺激增殖,而生长因子TGF-β(1-3)及其受体TGF-β RI和TGF-β RII参与抑制增殖。免疫组化检测方法和自动图像分析用于客观定量生长因子表达。数据表明,5戈伊照射后,在观察到绒毛的重大变化之前,在隐窝中发生生长刺激。然而,细胞数量减少、表达TGF-β(1-3)的细胞数量减少和绒毛中TGF-β(1-3)表达水平降低的组合可能导致隐窝细胞从调节性生长抑制中释放,并通过增加TGF-α和EGF的产生启动增殖刺激信号。增殖反应启动后的增殖调节似乎与隐窝中的生长因子EGF、TGF-α和TGF-β的关系比与绒毛细胞结构或生长因子表达的关系更密切,这支持了干细胞自动调节作为肠隐窝中细胞再生机制的概念。(C)1997年,辐射研究学会
The goal of the present study was to assess changes in proliferation in the mouse jejunum after irradiation and the role of the growth factors EGF, TGF-alpha and TGF-beta(1-3) in the proliferative response. Our working hypothesis was that feedback signals from the villus to cells in the crypt regulate proliferation, and that the growth factors EGF and TGF-alpha with their common receptor EGF-R are involved in stimulation of proliferation, while the growth factors TGF-beta(1-3) with their receptors TGF-beta RI and TGF-beta RII are involved in inhibition of proliferation during this regulation. Immunohistochemical detection methods and automated image analysis were used for objective quantification of growth factor expression. The data indicate that, after 5 Gy irradiation, growth stimulation in the crypts takes place before major changes in the villi are observed. However, the combination of the reduction in the cell number, the number of cells expressing TGF-beta(1-3) and the reduction in the level of expression of TGF-beta(1-3) in the villi may cause the release of crypt cells from regulatory growth inhibition and initiate a proliferation-stimulating signal by an increase in the production of TGF-alpha and EGF. Regulation of proliferation after initiation of a proliferative response seems to be related more to the growth factors EGF, TGF-alpha and TGF-beta, in the crypts than to villus cellularity or growth factor expression, supporting the concept of stem cell autoregulation as a mechanism of cell regeneration in the intestinal crypt. (C) 1997 by Radiation Research Society