分子时钟和损伤之间的相互调节
Carlos Rey-Serra1, Jessica Tituaña1, Terry Lin2
1Program of Physiological and Pathological Processes, Centro de Biología Molecular Severo Ochoa (CSIC-UAM), Madrid, Spain.
Life science alliance
|July 24, 2023
概括
脏损伤会破坏分子钟,导致代谢变化,使纤维化恶化. 缺少特定的时钟基因,Cry1和Cry2,严重增加了中性粒细胞的招募和纤维化严重程度.
科学领域:
- 腎臟病學 (nephrology) 是一種醫學專業.
- 分子生物学分子生物学
- 时间生物学 时间生物学
背景情况:
- 管间纤维化是慢性脏病的一个关键因素.
- 分子时钟在纤维化中的作用尚未完全理解.
研究的目的:
- 研究分子时钟与损伤/纤维化之间的关系.
- 探索时钟基因缺陷对损伤模型的影响.
主要方法:
- 使用损伤的小鼠模型 (单边尿路阻塞,叶酸,腺毒性).
- 使用了缺乏Bmal1,Clock,Cry1和Cry2时钟组件的转基因小鼠.
- 检查了用TGFβ治疗的人类管状上皮细胞.
主要成果:
- 分子时钟路径在受损的细胞和代谢改变中得到了丰富.
- 在人体管状上皮细胞中,TGFβ改变了时钟成分的表达.
- 缺少Cry1和Cry2通过促进中性粒细胞的招募和改变与代谢相关的基因表达来加剧纤维化.
结论:
- 脏损伤破坏了脏的外围分子钟.
- 被破坏的分子时钟促进了代谢失调,炎症和纤维化.
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