揭示了二二三氧化酶在血管生成过程中的作用
Marta Cecchi1, Cecilia Anceschi2, Angela Silvano3
1Department of Neuroscience, Psychology, Drug Research and Child Health, (NEUROFARBA) Pharmacology and Toxicology Section, University of Florence, 50139 Florence, Italy.
Pharmaceuticals (Basel, Switzerland)
|May 25, 2024
概括
二二氧化酶 (TDO) 在内皮细胞增殖和血管形成中起着关键作用. 抑制TDO损害了内皮细胞功能,这表明TDO在血管生成中起着新的作用.
科学领域:
- 内分泌学 在内分泌学.
- 免疫学 免疫学 免疫学
- 细胞生物学 细胞生物学
背景情况:
- 氨酸2,3-二氧化酶 (IDO1) 和二二氧化酶 (TDO) 是二代谢中的关键酶.
- 它们在免疫逃逸中的作用已经确立,但它们在血管生成中的参与尚不清楚.
- 这项研究研究了TDO和IDO1在人体内皮细胞中的表达和功能.
研究的目的:
- 描述TDO和IDO1在人类管静脉内皮细胞 (HUVEC) 和人类内皮形成殖民地细胞 (ECFC) 的表达和活性.
- 确定TDO和IDO1在内皮细胞增殖和血管生成中的作用.
主要方法:
- 定量逆转录-聚合酶链反应 (qRT-PCR) 和免疫光用于酶表达.
- 用ELISA测定测量酶活性.
- 通过MTT试验评估的细胞增殖;通过毛细血管形态发生体内血管生成.
主要成果:
- 在HUVEC和ECFC中表达TDO和IDO1.
- 选择性TDO抑制 (680C91) 显著损害了HUVEC增殖,3D管形成和VEGF诱导的mTOR酸化,而IDO1抑制没有影响.
- 抑制TDO还影响了ECFC形态发生,并减少了MMP9,c-Myc和E2f1的上调.
结论:
- 人体内皮细胞表达关键的金氨酸通路酶TDO和IDO1.
- 在体外,TDO对于内皮细胞增殖和毛细血管形态发生是至关重要的.
- 除了其免疫调节功能之外,TDO可能在血管生成中发挥着显著的病理生理作用.
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