GLP-2 stimulates colonic growth via KGF, released by subepithelial myofibroblasts with GLP-2 receptors
GLP-2 stimulates colonic growth via KGF, released by subepithelial myofibroblasts with GLP-2 receptors
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DOI：
10.1016/j.regpep.2004.07.009
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发表时间：
2005-01-15
影响因子：
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通讯作者：
Holst, JJ
中科院分区：
文献类型：
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作者：
Orskov, C;Hartmann, B;Holst, JJ
背景：胰高血糖素样肽 2 被认为是肠道的生长因子，但 GLP-2 受体的定位和对上皮生长的作用机制尚不清楚。方法和结果：我们通过免疫组织化学和原位杂交发现，胰高血糖素样肽-2 (GLP-2) 受体主要存在于大鼠、小鼠、狨猴和人小肠和大肠的上皮下成纤维细胞上。通过双标记，我们发现这些GLP-2受体免疫反应性细胞还产生平滑肌肌动蛋白和角质形成细胞生长因子（KGF）。通过在小鼠中皮下注射单独的GLP-2、GLP-2加KGF抗体、单独的KGF抗体或盐水，我们发现KGF抗体消除了GLP-2在大肠中的生长促进作用，但在小肠中没有。结论：我们的研究结果表明，肠道中的 GLP-2 通过激活上皮下肌成纤维细胞上的受体发挥作用，引起生长因子的释放，进而刺激肠道生长。 (C) 2004 Elsevier B.V 保留所有权利。
Background: Glucagon-like peptide-2 is thought to act as a growth factor for the gut, but the localization of the GLP-2 receptor and mechanism of action on epithelial growth is unclear. Methods and results: We found glucagon-like peptide-2 (GLP-2) receptors mainly on subepithelial rnyofibroblasts in rat, mouse, marmoset and human small and large intestine by immunohistochemistry and in situ hybridisation. By double labelling we found that these GLP-2 receptor immunoreactive cells also produce smooth muscle actin and keratinocyte growth factor (KGF).By subcutaneous infusion of either GLP-2 alone, GLP-2 plus KGF antibody, KGF antibody alone or saline in mice, we found that KGF antibody abolished the growth promoting effect of GLP-2 in the large intestine, but not in the small intestine. Conclusions: Our findings suggest that GLP-2 in the gut acts by activating receptors on the subepithelial myofibroblasts, causing the release of growth factors, which in turn stimulate intestinal growth. (C) 2004 Elsevier B.V All rights reserved.