HB-EGF promotes intestinal restitution by affecting integrin–extracellular matrix interactions and intercellular adhesions

HB-EGF promotes intestinal restitution by affecting integrin–extracellular matrix interactions and intercellular adhesions
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DOI:
10.3109/08977194.2012.755966
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发表时间:
2013-02
期刊:
影响因子:
1.8
通讯作者:
Yanwei Su;Ji-xin Yang;G. Besner
Yanwei Su;Ji-xin Yang;G. Besner
中科院分区:
生物学4区
文献类型:
--
作者:
Yanwei Su;Ji-xin Yang;G. Besner

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恢复是肠上皮细胞(IEC)愈合的关键形式。我们以前已经表明,肝素结合表皮样生长因子(HB-EGF)是必要的IEC恢复,然而,HB-EGF促进恢复的机制仍然知之甚少。本研究旨在研究HB-EGF是否通过影响整合素-细胞外基质(ECM)相互作用和细胞间粘附来促进肠道恢复。在小鼠坏死性小肠结肠炎(NEC)模型体内和IEC线刮伤愈合模型体外检查HB-EGF给药的效果。我们评估了HB-EGF对整合素、E-钙粘蛋白/β-连环蛋白和整合素α5β1依赖的细胞-ECM相互作用的表达的影响。我们发现,HB-EGF促进肠道重建和整合素α5β1的表达。HB-EGF促进整合素α5β1依赖的细胞粘附和铺展。另外,HB-EGF通过激活v-erb-b2红细胞白血病病毒癌基因同源物(ErbB-1),降低E-cadherin/β-catenin的表达。我们得出结论,HB-EGF通过影响整合素-ECM相互作用和细胞间粘附促进肠道恢复。
Restitution is a critical form of intestinal epithelial cell (IEC) healing. We have previously shown that heparin-binding epidermal-like growth factor (HB-EGF) is necessary for IEC restitution; however, the mechanisms by which HB-EGF promotes restitution remain poorly understood. This study was designed to investigate whether HB-EGF promotes intestinal restitution by affecting integrin–extracellular matrix (ECM) interactions and intercellular adhesions. The effect of HB-EGF administration was examined in a murine necrotizing enterocolitis (NEC) model in vivo and an IEC line scrape-wound healing model in vitro. We evaluated the effect of HB-EGF on the expression of integrins, E-cadherin/β-catenin, and integrin α5β1-dependent cell–ECM interactions. We found that HB-EGF promoted intestinal restitution and the expression of integrin α5β1. HB-EGF promoted integrin α5β1-dependent cell adhesion and spreading. In addition, HB-EGF decreased the expression E-cadherin/β-catenin, via the activation of v-erb-b2 erythroblastic leukemia viral oncogene homolog (ErbB-1). We conclude that HB-EGF promotes intestinal restitution by affecting integrin–ECM interactions and intercellular adhesions.