التفاصيل البيبلوغرافية
العنوان: |
Rack1‐mediated ferroptosis affects hindgut development in rats with anorectal malformations: Spatial transcriptome insights. |
المؤلفون: |
Wang, Chen‐Yi, Li, Mu‐Yu, Li, Si‐Ying, Wei, Xiao‐Gao, Dong, Nai‐Xuan, Liu, Shu‐Ting, Yuan, Zheng‐Wei, Li, Bo, Pierro, Agostino, Tang, Xiao‐Bing, Bai, Yu‐Zuo |
المصدر: |
Cell Proliferation; Jul2024, Vol. 57 Issue 7, p1-15, 15p |
مصطلحات موضوعية: |
TRANSCRIPTOMES, IRON ions, RATS, HUMAN abnormalities, ALIMENTARY canal, URODYNAMICS |
مستخلص: |
Anorectal malformation (ARM), a common congenital anomaly of the digestive tract, is a result of insufficient elongation of the urorectal septum. The cytoplasmic protein Receptor of Activated C‐Kinase 1 (Rack1) is involved in embryonic neural development; however, its role in embryonic digestive tract development and ARM formation is unexplored. Our study explored the hindgut development and cell death mechanisms in ARM‐affected rats using spatial transcriptome analysis. We induced ARM in rats by administering ethylenethiourea via gavage on gestational day (GD) 10. On GDs 14–16, embryos from both normal and ARM groups underwent spatial transcriptome sequencing, which identified key genes and signalling pathways. Rack1 exhibited significant interactions among differentially expressed genes on GDs 15 and 16. Reduced Rack1 expression in the ARM‐affected hindgut, verified by Rack1 silencing in intestinal epithelial cells, led to increased P38 phosphorylation and activation of the MAPK signalling pathway. The suppression of this pathway downregulated Nqo1 and Gpx4 expression, resulting in elevated intracellular levels of ferrous ions, reactive oxygen species (ROS) and lipid peroxides. Downregulation of Gpx4 expression in the ARM hindgut, coupled with Rack1 co‐localisation and consistent mitochondrial morphology, indicated ferroptosis. In summary, Rack1, acting as a hub gene, modulates ferrous ions, lipid peroxides, and ROS via the P38‐MAPK/Nqo1/Gpx4 axis. This modulation induces ferroptosis in intestinal epithelial cells, potentially influencing hindgut development during ARM onset. [ABSTRACT FROM AUTHOR] |
|
Copyright of Cell Proliferation is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.) |
قاعدة البيانات: |
Complementary Index |