肝素结合表皮生长因子样生长因子（HB-EGF）通过粘着斑激酶促进细胞迁移和黏附。
Heparin-binding EGF-like growth factor (HB-EGF) promotes cell migration and adhesion via focal adhesion kinase.
机构信息
Department of Cardiovascular and Respiratory Medicine, Wuhan Puai Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China; Department of Pediatric Surgery, Nationwide Children's Hospital, Center for Perinatal Research, The Research Institute at Nationwide Children's Hospital, The Ohio State University College of Medicine, Columbus, Ohio.
Department of Pediatric Surgery, Nationwide Children's Hospital, Center for Perinatal Research, The Research Institute at Nationwide Children's Hospital, The Ohio State University College of Medicine, Columbus, Ohio.
出版信息
J Surg Res. 2014 Jun 15;189(2):222-31. doi: 10.1016/j.jss.2014.02.055. Epub 2014 Mar 3.
BACKGROUND
Cell migration and adhesion are essential in intestinal epithelial wound healing and recovery from injury. Focal adhesion kinase (FAK) plays an important role in cell-extracellular matrix signal transduction. We have previously shown that heparin-binding EGF-like growth factor (HB-EGF) promotes intestinal epithelial cell (IEC) migration and adhesion in vitro. The present study was designed to determine whether FAK is involved in HB-EGF-induced IEC migration and adhesion.
MATERIALS AND METHODS
A scrape wound healing model of rat IECs was used to examine the effect of HB-EGF on FAK-dependent cell migration in vitro. Immunofluorescence and Western blot analyses were performed to evaluate the effect of HB-EGF on the expression of phosphorylated FAK (p-FAK). Cell adhesion assays were performed to determine the role of FAK in HB-EGF-induced cell adhesion on fibronectin (FN).
RESULTS
HB-EGF significantly increased healing after scrape wounding, an effect that was reversed in the presence of an FAK inhibitor 14 (both with P < 0.05). HB-EGF increased p-FAK expression and induced p-FAK redistribution and actin reorganization in migrating rat IECs. Cell adhesion and spreading on FN were significantly increased by HB-EGF (P < 0.05). FAK inhibitor 14 significantly inhibited both intrinsic and HB-EGF-induced cell adhesion and spreading on FN (both with P < 0.05).
CONCLUSIONS
FAK phosphorylation and FAK-mediated signal transduction play essential roles in HB-EGF-mediated IEC migration and adhesion.
背景
细胞迁移和黏附对于肠道上皮细胞的创伤愈合和损伤恢复至关重要。黏着斑激酶（FAK）在细胞-细胞外基质信号转导中发挥着重要作用。我们之前的研究表明，肝素结合表皮生长因子样生长因子（HB-EGF）可促进体外肠上皮细胞（IEC）的迁移和黏附。本研究旨在确定 FAK 是否参与 HB-EGF 诱导的 IEC 迁移和黏附。
材料和方法
采用大鼠 IEC 的划痕愈合模型，体外研究 HB-EGF 对 FAK 依赖性细胞迁移的影响。采用免疫荧光和 Western blot 分析评估 HB-EGF 对磷酸化 FAK（p-FAK）表达的影响。采用细胞黏附实验，确定 FAK 在 HB-EGF 诱导的纤维连接蛋白（FN）上细胞黏附中的作用。
结果
HB-EGF 显著促进了划痕损伤后的愈合，而 FAK 抑制剂 14 的存在则逆转了这一效应（均 P<0.05）。HB-EGF 增加了 p-FAK 的表达，并诱导了迁移大鼠 IEC 中 p-FAK 的重分布和肌动蛋白的重组。HB-EGF 显著增加了细胞在 FN 上的黏附和铺展（均 P<0.05）。FAK 抑制剂 14 显著抑制了内在和 HB-EGF 诱导的细胞在 FN 上的黏附和铺展（均 P<0.05）。
结论
FAK 磷酸化和 FAK 介导的信号转导在 HB-EGF 介导的 IEC 迁移和黏附中发挥着重要作用。
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