IOX1 protects from TGF‑β induced fibrosis in LX‑2 cells via the regulation of extracellular matrix protein expression

Tian,Tian; Xie,Rujia; Ding,Kaize; Han,Bing; Yang,Qin; Yang,Xue

doi:10.3892/etm.2021.9611

IOX1 protects from TGF‑β induced fibrosis in LX‑2 cells via the regulation of extracellular matrix protein expression

Authors:
- Tian Tian
- Rujia Xie
- Kaize Ding
- Bing Han
- Qin Yang
- Xue Yang
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Affiliations: Department of Eugenic Genetics, Guiyang Maternal and Child Health Care Hospital, Guiyang, Guizhou 550003, P.R. China, Department of Guizhou Provincial Key Laboratory of Pathogenesis and Drug Research on Common Chronic Diseases, Guizhou Medical University, Guiyang, Guizhou 550004, P.R. China, Department of Assisted Reproduction, Guiyang Maternal and Child Health Care Hospital, Guiyang, Guizhou 550003, P.R. China
Published online on: January 5, 2021 https://doi.org/10.3892/etm.2021.9611
Article Number: 180
Copyright: © Tian et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

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.

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