IOX1 protects from TGF‑β induced fibrosis in LX‑2 cells via the regulation of extracellular matrix protein expression
| Autor: | Ru-Jia Xie, Kaize Ding, Tian Tian, Xue Yang, Bing Han, Qin Yang |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Cancer Research extracellular matrix H3K9 dimethylation Cell Flow cytometry Extracellular matrix 03 medical and health sciences 0302 clinical medicine Immunology and Microbiology (miscellaneous) medicine hepatic fibrosis medicine.diagnostic_test Cell growth Chemistry Articles General Medicine Cell cycle Cell biology 030104 developmental biology medicine.anatomical_structure Apoptosis 030220 oncology & carcinogenesis IOX1 Chromatin immunoprecipitation Type I collagen |
| Zdroj: | Experimental and Therapeutic Medicine |
| ISSN: | 1792-1015 1792-0981 |
| DOI: | 10.3892/etm.2021.9611 |
| Popis: | The aim of the present study was to investigate the effect of the histone H3K9 demethylase inhibitor, IOX1, on the mechanism of hepatic fibrosis in TGF-β-induced human hepatic stellate LX-2 cells. Cellular proliferation, apoptosis, histone H3K9 dimethylation (H3K9me2), protein expression of extracellular matrix (ECM)-related proteins α-smooth muscle actin (SMA), type I collagen (Col I), MMP-1 and TIMP-1 were measured. H3K9me2 levels in the promoter region of ECM-related genes were detected by real-time cell analysis (RTCA), flow cytometry, western blotting and chromatin immunoprecipitation (ChIP) in LX-2 cells. IOX1 significantly inhibited cell proliferation and the IC50 of IOX1 was 100 µM in cells treated with IOX1 for 48 h. IOX1 significantly induced apoptosis in LX-2 cells in a concentration-dependent manner. In addition, different concentration of IOX1 increased the level of H3K9me2 and downregulated the expression of α-SMA, Col I, MMP-1 and TIMP-1 in TGF-β-induced LX-2 cells. ChIP measurements indicated that H3K9me2 levels in the promotor region of the corresponding genes were increased in TGF-β-induced LX-2 cells. IOX1 may elevate H3K9me2 in the promotor region of Col I, MMP-1, and TIMP-1 genes to regulate α-SMA, Col I, MMP-1 and TIMP-1 protein expression to induce cell apoptosis, inhibit LX-2 cell proliferation and oppose hepatic fibrotic activity. |
| Databáze: | OpenAIRE |
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