دورية أكاديمية
Sodium arsenite induces hepatic stellate cells activation by m6A modification of TGF-β1 during liver fibrosis
| العنوان: | Sodium arsenite induces hepatic stellate cells activation by m6A modification of TGF-β1 during liver fibrosis |
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| المؤلفون: | Tianming Qiu, Kun Hou, Jingyuan Zhang, Ningning Wang, Xiaofeng Yao, Guang Yang, Liping Jiang, Jikun Dong, Menglong Miao, Jie Bai, Xiance Sun |
| المصدر: | Ecotoxicology and Environmental Safety, Vol 278, Iss , Pp 116435- (2024) |
| بيانات النشر: | Elsevier, 2024. |
| سنة النشر: | 2024 |
| المجموعة: | LCC:Environmental pollution LCC:Environmental sciences |
| مصطلحات موضوعية: | Sodium arsenite, Hepatic stellate cells, N6-methyladenosine, TGF-β1, Smad signaling, Environmental pollution, TD172-193.5, Environmental sciences, GE1-350 |
| الوصف: | The compound known as Sodium arsenite (NaAsO2), which is a prevalent type of inorganic arsenic found in the environment, has been strongly associated with liver fibrosis (LF), a key characteristic of nonalcoholic fatty liver disease (NAFLD), which has been demonstrated in our previous study. Our previous research has shown that exposure to NaAsO2 triggers the activation of hepatic stellate cells (HSCs), a crucial event in the development of LF. However, the molecular mechanism is still unknown. N6-methyladenosine (m6A) modification is the most crucial post-transcriptional modification in liver disease. Nevertheless, the precise function of m6A alteration in triggering HSCs and initiating LF caused by NaAsO2 remains unknown. Here, we found that NaAsO2 induced LF and HSCs activation through TGF-β/Smad signaling, which could be reversed by TGF-β1 knockdown. Furthermore, NaAsO2 treatment enhanced the m6A modification level both in vivo and in vitro. Significantly, NaAsO2 promoted the specific interaction of METTL14 and IGF2BP2 with TGF-β1 and enhanced the TGF-β1 mRNA stability. Notably, NaAsO2-induced TGF-β/Smad pathway and HSC-t6 cells activation might be avoided by limiting METTL14/IGF2BP2-mediated m6A modification. Our findings showed that the NaAsO2-induced activation of HSCs and LF is made possible by the METTL14/IGF2BP2-mediated m6A methylation of TGF-β1, which may open up new therapeutic options for LF brought on by environmental hazards. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 0147-6513 |
| العلاقة: | http://www.sciencedirect.com/science/article/pii/S0147651324005116Test; https://doaj.org/toc/0147-6513Test |
| DOI: | 10.1016/j.ecoenv.2024.116435 |
| الوصول الحر: | https://doaj.org/article/30feb4f8b0b04e5293a252967761bb61Test |
| رقم الانضمام: | edsdoj.30feb4f8b0b04e5293a252967761bb61 |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 01476513 |
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| DOI: | 10.1016/j.ecoenv.2024.116435 |