胰高血糖素样肽-2促进细胞增殖、抑制细胞凋亡的分子机制

Molecular Mechanism of Glucagon Peptide-2 in Stimulating Cell Proliferation and Suppressing Cell Apoptosis

胰高血糖素样肽-2(GLP-2)是近年发现的一种由肠道L细胞分泌的功能性小肽,对胃肠道具有特异性的调节功能,能通过刺激肠细胞的增殖,抑制肠细胞凋亡和水解而增加肠绒毛高度、黏膜厚度及肠道重量等,进而影响肠道正常的结构和功能。GLP-2对肠细胞增殖、凋亡的调节涉及多种细胞信号传导途径,主要有G蛋白偶联的环化一磷酸腺苷/蛋白激酶A(cAMP/PKA)或磷脂酰肌醇-3激酶/Akt(PI-3K/Akt)途径、胰岛素样生长因子-1(IGF-1)参与的Wingless(Wnt)/β-连环蛋白(β-catenin)途径、酪氨酸蛋白激酶介导的细胞外信号调节激酶1/2(ERK1/2)等信号通路,其中以G蛋白偶联的信号途径为主要途径。这些途径相互协调,共同调控肠上皮细胞的稳态发育和肠道适应。本文将对GLP-2影响细胞增殖、凋亡的分子机制作一综述,为深入认识GLP-2的作用机理提供参考。

Glucagon peptide-2,synthesized in and then released from enteroendocrine L cell,is a functional peptide with strong and specific intestinotrophic function,which is mainly to increase intestinal villus height,mucosa thickness and intestinal weight and accommodate the ordinary intestinal structure and function via stimulating cell proliferation and suppressing cell apoptosis and hydrolysis.Many signal transduction pathways are involved in the effects of GLP-2 on intestinal cell proliferation and apoptosis,such as G-protein coupled cAMP/PKA,wingless（Wnt）signal pathways,PI-3K/Akt and ERK1/2,etc.Among these signal pathways,cAMP/PKA is the most important one,while others are supplementary for it.They jointly coordinate each other to regulate the steady development of enterocyte and intestinal adaptation.This article gives a review on the molecular mechanism of GLP-2 in the regulation of cell proliferation and apoptosis,providing a reference for further understanding of mechanism of GLP-2.