在血管新生调节中的SUMOylation细调内皮细胞HEY1
Ruizhe Ren1,2, Sha Ding1,2, Kefan Ma1,2
1Key Laboratory of Cardiovascular Intervention and Regenerative Medicine of Zhejiang Province of Sir Run Run Shaw Hospital, MOE Laboratory of Biosystems Homeostasis & Protection of College of Life Sciences, Zhejiang University, Hangzhou, China (R.R., S.D., K.M., Y.J., Yiran Wang, J.C., Yunyun Wang, Y.K., X.F., X.Z., C.Q., X.W., L.Y.).
Circulation research
|January 3, 2024
概括
转录因子HEY1的可逆SUMOylation微调其活性,控制血管生成. 这种翻译后修饰对于调节内皮细胞功能在正常发育和疾病中至关重要.
科学领域:
- 分子生物学分子生物学
- 发展生物学 发展生物学
- 细胞生物学 细胞生物学
背景情况:
- 血管新生对于胚胎发育和组织修复至关重要,由信号通路调节.
- 转录因子HEY1 (与YRPW动机相关的毛发/增强分裂) -1,是发育血管生成的关键.
- HEY1在血管生成中的确切机制尚不清楚,但翻译后SUMOylation可能起着调节作用.
研究的目的:
- 阐明 HEY1 SUMOylation 在血管生成中的生化特征和功能作用.
- 研究SUMOylation如何影响HEY1的DNA结合和二元化能力.
- 确定HEY1 SUMOylation对内皮细胞功能和血管生长的体内和体外影响.
主要方法:
- 生物化学试验 (免疫沉,质谱) 用于表征HEY1 SUMOylation.
- 染色体免疫沉和光酶测试以评估HEY1的促进体结合能力.
- 在体外基于细胞的测试 (伤口愈合,透孔) 和体内模型 (母体凝插头,视网膜病变,瘤血管生成) 来评估血管活性.
主要成果:
- HEY1在内皮细胞中经历SUMOylation,由TRIM28.8介导.
- SUMOylation 增强了 HEY1 的 DNA 结合和同质化,抑制了血管受体氨酸激酶 (RTK) 信号传递.
- 在益血管性刺激下脱SUMOylation导致HES1异体化和失去HEY1的抑制功能.
结论:
- 可逆HEY1 SUMOylation是协调内皮血管新生信号的关键机制.
- SUMOylation微调HEY1的转录活性,在生理和病理条件下影响血管生成.
- 这种修饰增强了HEY1在内皮细胞中的DNA结合和转录复合体形成.
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