Effect of GLP-2 on mucosal morphology and SGLT1 expression in tissue-engineered neointestine.
Effect of GLP-2 on mucosal morphology and SGLT1 expression in tissue-engineered neointestine.
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GLP-2 对组织工程新肠粘膜形态和 SGLT1 表达的影响。
DOI：
10.1152/ajpgi.00374.2002
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发表时间：
2003
期刊：
影响因子：
--
通讯作者：
Whang,EdwardE
中科院分区：
文献类型：
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作者：
Ramsanahie,Anthony;Duxbury,MarkS;Grikscheit,TracyC;Perez,Alexander;Rhoads,DavidB;Gardner-Thorpe,James;Ogilvie,Jennifer;Ashley,StanleyW;Vacanti,JosephP;Whang,EdwardE
利用组织工程技术，我们已经开发出一种新的肠，再生天然小肠的结构和动力学特征。在这项研究中，我们测试了新生肠对胰高血糖素样肽2（GLP-2）的反应性。通过用新生大鼠肠类器官单位接种生物可降解聚合物来工程化新生肠囊肿。使包囊成熟并与同系成年受体的天然空肠融合。动物用GLP-2 [Gly 2]（每日两次，1 μ g/g体重）或单独的溶媒（对照）处理10天。然后处死大鼠，收获组织用于分析。采用北方印迹和原位杂交检测钠-葡萄糖协同转运蛋白1（SGLT 1）mRNA的表达。免疫荧光法定位SGLT 1蛋白。GLP-2给药导致新生肠绒毛高度和隐窝深度分别增加1.8倍和1.7倍（P <0.05）。GLP-2给药还导致新黏蛋白SGLT 1 mRNA表达增加2.4倍（P <0.01）。SGLT 1 mRNA表达定位于整个绒毛中的肠上皮细胞，SGLT 1蛋白定位于GLP-2给药动物新生肠中沿整个绒毛长度沿着肠上皮细胞的刷状缘。组织工程化新肠对外源性GLP-2的反应包括粘膜生长和SGLT 1表达增强。因此，组织工程的原则可能有助于解剖的调节机制介导的复杂过程中的肠上皮细胞。
Using tissue-engineering techniques, we have developed a neointestine that regenerates the structural and dynamic features of native small intestine. In this study, we tested neointestinal responsiveness to glucagon-like peptide 2 (GLP-2). Neointestinal cysts were engineered by seeding biodegradable polymers with neonatal rat intestinal organoid units. The cysts were matured and anastomosed to the native jejunum of syngeneic adult recipients. Animals were treated with GLP-2 [Gly2] (twice daily, 1 μg/g body wt) or vehicle alone (control) for 10 days. Rats were then killed, and tissues were harvested for analysis. Na+-glucose cotransporter (SGLT1) mRNA expression was assessed with Northern blotting and in situ hybridization. SGLT1 protein was localized by using immunofluorescence. GLP-2 administration resulted in 1.8- and 1.7-fold increases (P< 0.05) in neointestinal villus height and crypt depth, respectively. GLP-2 administration also resulted in a 2.4-fold increase (P< 0.01) in neomucosal SGLT1 mRNA expression. SGLT1 mRNA expression was localized to enterocytes throughout the villi, and SGLT1 protein was localized to the brush border of enterocytes along the entire length of villi from the neointestine of GLP-2-treated animals. The response of tissue-engineered neointestine to exogenous GLP-2 includes mucosal growth and enhanced SGLT1 expression. Therefore, tissue-engineering principles may help in dissecting the regulatory mechanisms mediating complex processes in the intestinal epithelium.