Oxidative stress promotes liver fibrosis by modulating the microRNA-144 and SIN3A-p38 pathways in hepatic stellate cells
文献类型：期刊论文
| 作者 | Hao, Yawen10,11; Song, Shaohua8,9; Li, Tao8,9; Zai, Qiuhong10,11; Ma, Ningning10,11; Li, Yixin7; Yang, Liu10,11; Xiao, Peng6; Xu, Tianyue11; Ji, Longshan5 |
| 刊名 | INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES
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| 出版日期 | 2024 |
| 卷号 | 20期号:7页码:2422-2439 |
| 关键词 | AAV6 ROS HSC p38 liver fibrogenesis |
| ISSN号 | 1449-2288 |
| DOI | 10.7150/ijbs.92749 |
| 通讯作者 | Xie, Qing(xieqingrjh@163.com) ; He, Yong(heyong@simm.ac.cn) |
| 英文摘要 | Background & Aims : Reactive oxygen species (ROS) act as modulators triggering cellular dysfunctions and organ damage including liver fibrosis in which hepatic stellate cell (HSC) activation plays a key role. Previous studies suggest that microRNA-144 (miR-144) acts as a pro-oxidant molecule; however, whether and how miR-144 affects HSC activation and liver fibrosis remain unknown. Methods: Carbon tetrachloride (CCl 4 ) and bile duct ligation (BDL)-induced experimental liver fibrosis models were used. Hepatic miR-144 expression was analyzed by miRNA in situ hybridization with RNAscope probe. The in vivo effects of silencing or overexpressing miR-144 were examined with an adeno-associated virus 6 (AAV6) carrying miR-144 inhibitor or mimics in fibrotic mouse experimental models. Results: In this study, we demonstrated that ROS treatment significantly upregulated miR-144 in HSCs, which further promoted HSC activation in vitro . Interestingly, miR-144 was preferentially elevated in HSCs of experimental liver fibrosis in mice and in human liver fibrotic tissues. Furthermore, in vivo loss or gain-of-function experiments via AAV6 carrying miR-144 antagomir or agomir revealed that blockade of miR-144 in HSCs mitigated, while overexpression of miR-144 in HSCs accelerated the development of experimental liver fibrosis. Mechanistically, SIN3 transcription regulator family member A (SIN3A), a transcriptional repressor, was identified to be the target of miR-144 in HSCs. MiR-144 downregulated Sin3A , and in line with this result, specific knockdown of Sin3a in HSCs remarkedly activated p38 MAPK signaling pathway to promote HSC activation, eventually exacerbating liver fibrosis. Conclusions: Oxidative stress -driven miR-144 fuels HSC activation and liver fibrogenesis by limiting the SIN3A-p38 axis. Thus, a specific inhibition of miR-144 in HSCs could be a novel therapeutic strategy for the treatment of liver fibrosis. |
| WOS关键词 | ACTIVATION ; EXPRESSION ; MOUSE |
| 资助项目 | Natural Science Foundation of China[82270601] ; Natural Science Foundation of China[82270596] ; Shanghai Pujiang Program[21PJ1415400] ; Natural Science Foundation of Shanghai[22ZR1473800] |
| WOS研究方向 | Biochemistry & Molecular Biology ; Life Sciences & Biomedicine - Other Topics |
| 语种 | 英语 |
| WOS记录号 | WOS:001229795500023 |
| 出版者 | IVYSPRING INT PUBL |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/311081]  |
| 专题 | 中国科学院上海药物研究所 |
| 通讯作者 | Xie, Qing; He, Yong |
| 作者单位 | 1.Shanghai Jiao Tong Univ, Sch Med, Ruijin Hosp, Dept Infect Dis,Translat Lab Liver Dis, Shanghai 200025, Peoples R China 2.Inst Univ France IUF, F-75005 Paris 05, France 3.Univ Paris Est Creteil UPEC, F-94000 Creteil, France 4.Med Klin MS Hepatol & Gastroenterol, Charite Univ Med Berlin, Berlin, Germany 5.Shanghai Univ Tradit Chinese Med, Shuguang Hosp, Lab Cellular Immun, Shanghai Key Lab Tradit Chinese Med, Shanghai, Peoples R China 6.Jilin Univ, First Hosp Jilin Univ, Dept Hepatol, Changchun, Peoples R China 7.Univ Sci & Technol China USTC, Affiliated Hosp USTC 1, Dept Cardiol, Div Life Sci & Med, Hefei, Peoples R China 8.Shanghai Jiao Tong Univ, Ruijin Hosp, Sch Med, Dept Infect Dis, Shanghai, Peoples R China 9.Shanghai Jiao Tong Univ, Ruijin Hosp, Sch Med, Dept Gen Surg, Shanghai, Peoples R China 10.Univ Chinese Acad Sci, Beijing, Peoples R China |
| 推荐引用方式 GB/T 7714 | Hao, Yawen,Song, Shaohua,Li, Tao,et al. Oxidative stress promotes liver fibrosis by modulating the microRNA-144 and SIN3A-p38 pathways in hepatic stellate cells[J]. INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES,2024,20(7):2422-2439. |
| APA | Hao, Yawen.,Song, Shaohua.,Li, Tao.,Zai, Qiuhong.,Ma, Ningning.,...&He, Yong.(2024).Oxidative stress promotes liver fibrosis by modulating the microRNA-144 and SIN3A-p38 pathways in hepatic stellate cells.INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES,20(7),2422-2439. |
| MLA | Hao, Yawen,et al."Oxidative stress promotes liver fibrosis by modulating the microRNA-144 and SIN3A-p38 pathways in hepatic stellate cells".INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES 20.7(2024):2422-2439. |
入库方式： OAI收割
来源：上海药物研究所
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