SUMO化调节HIF1α活性作用于创伤愈合中血管新生的分子机制

Angiogenesis is essential for wound healing. Hypoxia-inducible factor1（HIF1）modulates wound angiogenesis, conceivably via up-regulating VEGF. However, the mechanisms for stabilization of HIF1 after transcription in wound angiogenesis are not fully understood. Our previous work shows an increase SUMOylation of HIF1alpha induced by wound hypoxia. In addition, we find the level of VEGF rises after skin excision, which associated with wound angiogenesis. Our data indicate that SUMOylation of HIF1 might play a key role in up-regulation of VEGF and wound angiogenesis. Therefore, in this study, dynamic changes between SUMOylation and deSUMOylation of HIF1alpha during wound healing will be studied. We will explore whether the change of SUMOylation and deSUMOylation of HIF1alpha regulates production of VEGF. Finally, we will testify that SUMOylation/deSUMOylation of HIF1 plays a key role in induction of angiogenesis through up-regulation of VEGF during wound healing process.

HIF1过上调VEGF调节血管新生，但创伤愈合中 HIF1如何不被蛋白酶降解来维持其活性有待阐明。本课题组在前期工作中发现损伤后低氧诱导的HIF1α蛋白SUMO化修饰有动态变化; 还发现损伤愈合过程中VEGF的含量增加与血管新生成正性相关。提示损伤后SUMO化修饰可能调节HIF1α蛋白的稳定性，进而可调节VEGF的促血管生成作用。在此基础上，拟探讨创伤后低氧诱导的SUMO化修饰HIF1α蛋白和去SUMO化的动态变化；明确SUMO化／去SUMO化修饰HIF1α蛋白对调控VEGF的作用；证实SUMO化／去SUMO化HIF1α－VEGF－Angiogenesis的为创伤愈合过程中血管新生的分子机制。

HIF1过上调VEGF调节血管新生，但创伤愈合中 HIF1如何不被蛋白酶降解来维持其活性有待阐明。本课题组在前期工作中发现损伤后低氧诱导的HIF1α蛋白SUMO化修饰有动态变化; 还发现损伤愈合过程中VEGF的含量增加与血管新生成正性相关。提示损伤后SUMO化修饰可能调节HIF1α蛋白的稳定性，进而可调节VEGF的促血管生成作用。本研究主要探讨创伤后低氧诱导的SUMO化修饰HIF1α蛋白和去SUMO化的动态变化；明确SUMO化／去SUMO化修饰HIF1α蛋白对调控VEGF的作用；证实SUMO化／去SUMO化HIF1α－VEGF－Angiogenesis的为创伤愈合过程中血管新生的分子机制。通过完成以上研究，有望进一步阐明创伤愈合过程中血管新生的分子机制, 从而为促进创伤愈合的治疗提供新靶点，具有重要的理论价值和临床意义。