素和骨形态遗传蛋白在人类上皮层细胞的类固醇生成中的相互作用
Yoshiaki Soejima1, Nahoko Iwata1, Ran Nishioka1
1Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kitaku, Okayama 700-8558, Japan.
International journal of molecular sciences
|August 26, 2023
概括
素A和骨形态遗传蛋白-6 (BMP-6) 增强人体细胞中的上腺类固醇生成. 这些通路相互作用,相互抑制对方,以微调上腺功能.
科学领域:
- 内分泌学 在内分泌学.
- 神经内分泌学神经内分泌学
- 分子生物学分子生物学
背景情况:
- 素是神经对中枢神经系统功能,如睡眠和食欲至关重要.
- 素受体存在于周围组织中,包括内分泌系统,这表明其作用更广泛.
- 骨形态遗传蛋白 (BMP) 是已知的上皮层中类固醇生成的调节者.
研究的目的:
- 为了研究上腺类固醇生成中素的作用.
- 探索人类上腺皮细胞中素和BMP信号传递之间的相互作用.
- 阐明素调节上腺类固醇生产的机制.
主要方法:
- 使用了人类上腺皮层的H295R细胞.
- 评估了类固醇酶 (StAR,CYP11B2,CYP17,HSD3B1) 和信号分子 (Smad1/5/9,Id-1,Smad7,BMP-6,ActRII,OX1R,OX2R) 的mRNA水平.
- 用素A和福斯科林刺激细胞,并测量下游信号事件和基因表达.
主要成果:
- 奥雷辛A治疗增加了关键类固醇生成酶的mRNA水平.
- 奥雷辛A增强了福斯科林诱导的类固醇酶表达.
- 奥雷辛A通过Smad7上调抑制了BMP受体信号传递 (Smad1/5/9酸化,Id-1).
- 奥雷辛A降低了BMP-6的表达和增加了ActRII的表达.
- 在BMP-6治疗下调了OX1RmRNA水平.
结论:
- 素和BMP-6都在人类细胞中刺激上腺皮质类固醇生成.
- 素和BMP-6信号通路表现出相互抑制.
- 这种相互相互作用允许对上腺类固醇生成进行微调.
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