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

第一作者： Lu, Xing

作者： Lu, Xing;Jiang, Ming;Tian, Juan;Liu, Wei;Wu, Fan;Yu, Lijuan;Wen, Hua;Feng, Guohui;Zhong, Shan;Xiang, Ying;Zhong, Shan

作者机构：

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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