CREB-H是早期产后发育期间肝素基因表达的压力调节剂
Chiara Vecchi1, Giuliana Montosi2, Cinzia Garuti2
1Department of Medical and Surgical Sciences for Children and Adults, University of Modena and Reggio Emilia, University Hospital of Modena, 41125, Modena, Italy. chiara.vecchi@unimore.it.
Journal of molecular medicine (Berlin, Germany)
|July 26, 2023
概括
循环AMP响应元素结合蛋白3样3 (CREB-H) 通过控制肝素的表达来调节铁的稳态. 失去CREB-H会导致年轻小鼠的铁过载,突出其在发展和压力期间维持铁平衡中的作用.
科学领域:
- 分子生物学分子生物学
- 遗传学 是一个遗传学.
- 生理学 生理学 生理学
- 营养生物化学 营养生物化学
背景情况:
- 肝素是铁平衡的主要调节剂,由肝脏产生.
- 循环AMP-响应性元素结合蛋白3样3 (CREB-H) 是已知的葡萄糖和脂质肝脏平衡的调节者.
- CREB-H已与肝素对病理性压力的反应有关.
研究的目的:
- 通过肝素调节,研究CREB-H在铁稳定中的生理作用.
- 检查早期产后发育期间野生类型和CREB-H淘汰赛小鼠的肝素基因表达和调节.
- 评估铁挑战和BMP6刺激对在CREB-H存在或不存在的情况下对肝素调节的影响.
主要方法:
- 在出生后发育过程中对野生型和Creb3l3淘汰赛小鼠的肝素基因表达的分析.
- 在体内铁挑战研究和体内BMP6刺激试验.
- 在CREB3L3沉默或HepG2细胞中促体突变后,研究BMP/SMAD信号通路和肝素促体活性.
主要成果:
- 在Creb3l3淘汰赛小鼠中,由于肝素mRNA的表达受损,在断奶后呈现出显著的血清和肝脏铁积累,在成年后正常化.
- 尽管BMP/SMAD信号完好无损,但在铁挑战期间,肝素基因表达在淘汰的小鼠中减少,导致肝脏铁的积累更大.
- 在CREB-H淘汰肝细胞和具有CREB-H淘汰或突变结合部位的HepG2细胞中,BMP6诱导的肝素基因反应被削弱.
结论:
- 在关键的出生后早期期间,CREB-H通过肝素调节在维持铁平衡方面发挥着至关重要的作用.
- CREB-H对于适当的肝素基因对铁挑战的反应至关重要,作为一个关键的压力传感器.
- 这项研究确定了CREB-H作为一种重要的转录因子,可以控制肝素基因表达在生理和病理生理状态.
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