缺氧诱导的P4HA1过度表达通过通过降低FBP1调节来增强内皮糖解,促进后缺血性血管生成
Yating Xu1,2, Di Xia1,3, Kai Huang4,5,6,7
1Clinic Center of Human Gene Research, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Ave, Wuhan, 430022, China.
Journal of translational medicine
|January 18, 2024
概括
普4-基酶亚单元α1 (P4HA1) 通过增强糖解促进缺血性疾病中的血管生成. 这一途径涉及P4HA1,α-甲酸盐,TET2和FBP1,为组织修复提供治疗潜力.
科学领域:
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
- 生物化学 生物化学
背景情况:
- 血管新生对于修复缺血组织至关重要,并且依赖于糖解来获得能量.
- 甲基4-基酶子单元α1 (P4HA1) 与癌症中的糖解有关,但其在血管生成中的作用尚不清楚.
研究的目的:
- 研究P4HA1在糖溶解诱导的血管生成中的作用,特别是在缺血性疾病的背景下.
- 阐明P4HA1影响内皮细胞功能和血管形成的分子机制.
主要方法:
- 在内皮细胞中通过腺病毒调节P4HA1表达.
- 在体外测试 (EDU结合,穿孔迁移,管形成) 和体内后肢缺血 (HLI) 模型来评估血管生成.
- 糖分离应激测试,葡萄糖吸收,乳酸盐生产,转录组测序,西部涂抹和RT-PCR用于分析代谢途径和分子机制.
主要成果:
- 在低氧和HLI模型下,P4HA1表达在内皮细胞中被上调.
- 在体外和体内,P4HA1的过度表达促进了血管生成,而 knockdown则抑制了它.
- P4HA1降低了α-甲酸盐 (α-KG),导致TET2蛋白和FBP1表达的降低,从而增强糖解和促进血管生成.
结论:
- 缺氧诱导的P4HA1过度表达通过通过P4HA1/α-KG/TET2/FBP1通路重新编程糖解质代谢来增强血管生成.
- P4HA1在缺血后血管生成中起着重要作用,是改善组织修复的潜在治疗点.
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