Proteomic analysis of cyclopamine effect on liver regeneration
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摘要: 目的 研究环靶明对肝再生的影响，并探讨其可能的分子作用机制。 方法 应用8标同位素标记相对和绝对定量（isobaric tags for relative and absolute quantification，iTRAQ）技术，结合二维液相色谱串联质谱（two-dimensional liquid chromatography-tandem mass spectrometry，2D LC-MS/MS）系统，以部分肝切除的大鼠为模型，全面分析了再生早期（12 h）环靶明干预组，肝脏蛋白质的表达差异。 结果 共鉴定1625种蛋白质，其中肝再生组有367种蛋白质的表达量与对照组（手术切下的正常肝组织）有显著差异，差异蛋白通路分析基因本体（gene ontology，GO）显示hedgehog（HH）信号通路激活，在肝再生过程中作用显著，其中的SHH、Gli2蛋白可能通过影响细胞凋亡和能量供给等方式参与肝再生调控，而环靶明干预组中这一通路未被激化，关键蛋白SHH，Gli2蛋白表达量下调。 结论 环靶明通过抑制HH信号通路中关键蛋白的表达影响肝再生，HH信号通路在肝细胞再生过程中具有重要作用。
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关键词:
- 环靶明 /
- 肝损伤与肝再生 /
- Hedgehog(HH)信号通路 /
- iTRAQ
Abstract: Objective To study the effect of cyclopamine on liver regeneration, and to explore its possible molecular mechanism. Methods iTRAQ-based quantitative proteomics combined with 2D liquid chromatography-tandem mass spectrometry were applied to study the protein expression of liver regeneration in rats with partial hepatectomy. Results A total of 1625 proteins were identified. 367 proteins were significantly different in the control group, cyclopamine-treated group and the partial hepatectomy group. The pathway analysis suggested that Hedgehog (HH) signaling pathway was activated in the partial hepatectomy group, and SHH, Gli2 in this pathway may participate in the regulation of liver regeneration by affecting apoptosis and energy supply. While SHH and Gli2 were down regulated in the cyclopamine group. Conclusion Cyclopamine inhibited by Hedgehog (HH) key protein signaling affects the expression of liver regeneration; Hedgehog (HH) signal pathway in the process of liver regeneration has an important role.-
Key words:
- cyclopamine /
- liver injury and liver regeneration /
- hedgehog (HH) signal pathway /
- iTRAQ
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