Growth Arrest-Specific Transcript 5 (GAS5) Exerts Important Roles on the Treatment of BM45 Cells of Liver Cirrhosis

• Main Authors: Xing Lu (Author), Ming Jiang (Author), Juan Tian (Author), Wei Liu (Author), Fan Wu (Author), Lijuan Yu (Author), Guohui Feng (Author), Shan Zhong (Author), Ying Xiang (Author), Hua Wen (Author)
• Format: Book
• Published: Elsevier, 2020-12-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.
• Notes: 2162-2531; 10.1016/j.omtn.2020.10.024
• Keywords: liver cirrhosis; growth arrest-specific transcript 5; bone marrow (BM)-derived CD45 cells; hepatic stellate cells; MMP-9; p27; Therapeutics. Pharmacology; RM1-950
• Source: Molecular Therapy: Nucleic Acids, Vol 22, Iss , Pp 1154-1163 (2020)

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)-β-induced dysregulation of miR-222, p27, and α-smooth muscle actin (α-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 α-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.