Growth Arrest-Specific Transcript 5 (GAS5) Exerts Important Roles on the Treatment of BM45 Cells of Liver Cirrhosis
文献类型： 外文期刊
作者： Lu, Xing 1 ; Jiang, Ming 1 ; Tian, Juan 1 ; Liu, Wei 1 ; Wu, Fan 1 ; Yu, Lijuan 1 ; Feng, Guohui 2 ; Zhong, Shan 2 ; Xiang, 1 ;
作者机构： 1.Chinese Acad Fishery Sci, Key Lab Freshwater Biodivers Conservat, Minist Agr & Rural Affairs, Yangtze River Fisheries Res Inst, Wuhan 430223, Hubei, Peoples R China
2.Wuhan Univ, Sch Basic Med Sci, Wuhan 430071, Hubei, Peoples R China
3.Hubei Prov Key Lab Allergy & Immunol, Wuhan 430071, Hubei, Peoples R China
期刊名称：MOLECULAR THERAPY-NUCLEIC ACIDS （ 影响因子：8.886； 五年影响因子：8.334 ）
ISSN： 2162-2531
年卷期： 2020 年 22 卷
页码：
收录情况： SCI
摘要： Bone marrow (BM)-derived CD45 (BM45) cells were demonstrated to exhibit an improved antifibrotic effect on the treatment of CCL4-induced liver fibrosis by significantly increasing the level of matrix metalloproteinase 9 (MMP-9). In this study, we aimed to validate the therapeutic effect of BM45 on the treatment of liver cirrhosis and to further investigate the molecular mechanism underlying the effect of growth arrest-specific transcript 5 (GAS5) on BM45. Accordingly, GAS5 significantly suppressed miR-222 and miR-21 expression but enhanced p27 and MMP-9 expression in HepG2 and LX2 cells. Additionally, GAS5 obstructed transforming growth factor (TGF)-beta-induced dysregulation of miR-222, p27, and alpha-smooth muscle actin (alpha-SMA) in mice. GAS5 showed a considerable potential to enhance the capability of BM45 in restoring the normal expression of CCL4, miR-222, miR-21, MMP-9, p27, and alpha-SMA that was dysregulated by alanine aminotransferase (ALT), albumin, and fibrosis. In summary, our study validated the regulatory relationship between miR-21 and MMP-9, as well as between miR-222 and p27. The overexpression of GAS5 upregulated the expression of MMP-9 and p27 via respectively reducing the miR-222 and miR-21 expression, resulting in higher BM45-induced activation of hepatic stellate cells (HSCs). Accordingly, same results were obtained in an animal model, indicating that GAS5 may exert a positive effect on the treatment of BM45 of liver cirrhosis.
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