5-methoxytryptophan alleviates liver fibrosis by modulating FOXO3a/miR-21/ATG5 signaling pathway mediated autophagy
| Autor: | Yimin Zhu, Ming Tong, Shi–Gang Tang, Yihe Lin, Meng Liu, Liang Chen, Qing Zheng |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Liver Cirrhosis
Male 0301 basic medicine Cell Survival ATG5 Autophagy-Related Protein 5 Cell Line Rats Sprague-Dawley 03 medical and health sciences 0302 clinical medicine In vivo Autophagy Hepatic Stellate Cells Animals Humans Carbon Tetrachloride Molecular Biology Dose-Response Relationship Drug biology Forkhead Box Protein O3 Tryptophan Cell Biology SMA In vitro Rats Fibronectin MicroRNAs 030104 developmental biology 030220 oncology & carcinogenesis Cancer research biology.protein Signal transduction Hepatic fibrosis Signal Transduction Research Paper Developmental Biology |
| Zdroj: | Cell Cycle |
| ISSN: | 1551-4005 1538-4101 |
| DOI: | 10.1080/15384101.2021.1897241 |
| Popis: | Liver fibrosis is a critical health issue in the world due to its rapidly increasing prevalence. It is of great demand to develop effective drugs for the treatment of liver fibrosis. 5-methoxytryptophan (5-MTP) has been reported to play an important role in anti-inflammatory, anti-cancer, myocardial-protective effects. However, the anti-fibrotic effect of 5-MTP is never covered in liver. Here, we investigated anti-fibrotic effects of 5-MTP on liver fibrosis and its underlying mechanism. In vitro, 5-MTP treatment could inhibit TGF-β1-induced elevated levels of collagen I, collagen III, fibronectin and α-smooth muscle actin (SMA) by stimulating autophagy process. Mechanically, the expression of FOXO3a was enhanced by 5-MTP and then repressed the level of miR-21, eventually leading to a restoration of autophagy-related gene ATG5. Furthermore, rescue experiments showed 5-MTP could activate autophagy process and suppress the activation of LX-2 cells by regulating FOXO3a/miR-21/ATG5 pathway. Consistently, 5-MTP significantly attenuated CCl4-induced hepatic fibrosis in rat model. In conclusion, our research discovered that 5-MTP effectively alleviated liver fibrosis in vitro and in vivo, which provided new insights into the application of 5-MTP for liver fibrosis. |
| Databáze: | OpenAIRE |
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