Hepatocyte growth factor promotes colonic epithelial regeneration via Akt signaling
Hepatocyte growth factor promotes colonic epithelial regeneration via Akt signaling
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DOI：
10.1152/ajpgi.00068.2007
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发表时间：
2007-07-01
影响因子：
4.5
通讯作者：
Sugiyama, Toshiro
中科院分区：
文献类型：
--
作者：
Kanayama, Masami;Takahara, Terumi;Sugiyama, Toshiro
肝细胞生长因子（HGF）可以促进损伤器官的再生，包括电穿孔（EP）基因治疗肝损伤。本研究旨在探讨肝细胞生长因子对葡聚糖硫酸钠诱导的结肠炎的影响，并试图阐明结肠上皮细胞的再生机制及其相关的信号通路。用葡聚糖硫酸钠诱导小鼠结肠炎模型，同时用EP转HGF基因。在第10天，通过组织学和蛋白质印迹分析评价结肠炎。用HGF蛋白处理结肠上皮细胞系MCE 301，观察其增殖和激活的信号通路。在体内，与对照组相比，HGF治疗组小鼠的组织学评分改善，Ki- 67阳性上皮细胞数量增加。Western印迹分析显示，与对照组相比，HGF处理组小鼠磷酸化Akt的表达增强.体外实验表明，HGF能促进MCE 301细胞的增殖。HGF刺激后磷酸化Akt表达增强超过48 h，尽管磷酸化ERK 1/ 2仅增强10 min。LY- 294002或Akt小干扰RNA抑制HGF诱导的细胞增殖。因此，HGF通过磷脂酰肌醇3-激酶/ Akt信号通路诱导结肠上皮细胞增殖。HGF基因治疗可通过PI 3 K/ Akt途径促进上皮细胞增殖来减轻急性结肠炎。这些数据表明，通过EP的HGF基因治疗可能是有效的炎症性肠病损伤的上皮细胞的再生和修复。
Hepatocyte growth factor ( HGF) can promote the regeneration of injured organs, including HGF gene therapy by electroporation ( EP) for liver injury. In this study, we investigated the effect of HGF on dextran sulfate sodium- induced colitis and tried to clarify the regenerative mechanisms of colonic epithelial cells and the signaling pathway involved. Colitis was induced by dextran sulfate sodium in mice, together with HGF gene transfer by EP. On day 10, the colitis was evaluated histologically and by Western blot analysis. The colonic epithelial cell line MCE301 was exposed to HGF protein, and its proliferation and activated signaling pathway were analyzed. In vivo, the histological score improved and the number of Ki- 67- positive epithelial cells increased in the HGF-treated mice compared with the controls. Western blot analysis showed enhanced expression of phospho- Akt in the HGF- treated mice compared with the controls. In vitro, HGF stimulated the proliferation of MCE301 cells. There was enhanced phospho- Akt expression for more than 48 h after HGF stimulation, although phospho- ERK1/ 2 was enhanced for only 10 min. LY- 294002 or Akt small interfering RNA suppressed cell proliferation induced by HGF. Thus HGF induces the proliferation of colonic epithelial cells via the phosphatidylinositol 3- kinase/ Akt signaling pathway. HGF gene therapy can attenuate acute colitis via epithelial cell proliferation through the PI3K/ Akt pathway. These data suggested that HGF gene therapy by EP may be effective for the regeneration and repair of injured epithelial cells in inflammatory bowel disease.