التفاصيل البيبلوغرافية
| العنوان: |
Alleviation of liver fibrosis by inhibiting a non-canonical ATF4-regulated enhancer program in hepatic stellate cells |
| المؤلفون: |
Li-Xian Yang, Chuangye Qi, Si Lu, Xiang-Shi Ye, Parnaz Merikhian, Du-Yu Zhang, Tao Yao, Jiang-Sha Zhao, Ying Wu, Yongshi Jia, Bo Shan, Jinghai Chen, Xiaozhou Mou, Jia You, Wenbo Li, Yu-Xiong Feng |
| المصدر: |
Nature Communications, Vol 16, Iss 1, Pp 1-15 (2025) |
| بيانات النشر: |
Nature Portfolio, 2025. |
| سنة النشر: |
2025 |
| المجموعة: |
LCC:Science |
| مصطلحات موضوعية: |
Science |
| الوصف: |
Abstract Liver fibrosis is a critical liver disease that can progress to more severe manifestations, such as cirrhosis, yet no effective targeted therapies are available. Here, we identify that ATF4, a master transcription factor in ER stress response, promotes liver fibrosis by facilitating a stress response-independent epigenetic program in hepatic stellate cells (HSCs). Unlike its canonical role in regulating UPR genes during ER stress, ATF4 activates epithelial-mesenchymal transition (EMT) gene transcription under fibrogenic conditions. HSC-specific depletion of ATF4 suppresses liver fibrosis in vivo. Mechanistically, TGFβ resets ATF4 to orchestrate a unique enhancer program for the transcriptional activation of pro-fibrotic EMT genes. Analysis of human data confirms a strong correlation between HSC ATF4 expression and liver fibrosis progression. Importantly, a small molecule inhibitor targeting ATF4 translation effectively mitigates liver fibrosis. Together, our findings identify a mechanism promoting liver fibrosis and reveal new opportunities for treating this otherwise non-targetable disease. |
| نوع الوثيقة: |
article |
| وصف الملف: |
electronic resource |
| اللغة: |
English |
| تدمد: |
2041-1723 |
| Relation: |
https://doaj.org/toc/2041-1723 |
| DOI: |
10.1038/s41467-024-55738-1 |
| URL الوصول: |
https://doaj.org/article/a9e7e767ade542d4932fd2e4a3918231 |
| رقم الانضمام: |
edsdoj.9e7e767ade542d4932fd2e4a3918231 |
| قاعدة البيانات: |
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