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Article Open Access

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
  • View Affiliations / Copyright

    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
    Copyright: © Tian et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 180
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    Published online on: January 5, 2021
       https://doi.org/10.3892/etm.2021.9611
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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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1 

Lei W, Long Y, Li S, Liu Z, Zhu F, Hou FF and Nie J: Homocysteine induces collagen I expression by downregulating histone methyltransferase G9a. PLoS One. 10(e0130421)2015.PubMed/NCBI View Article : Google Scholar

2 

Sowa Y and Sakai T: Development of novel epigenetic molecular-targeting agents. Nihon Rinsho. 73:1263–1267. 2015.PubMed/NCBI(In Japanese).

3 

Füllgrabe J, Heldring N, Hermanson O and Joseph B: Cracking the survival code: Autophagy-related histone modifications. Autophagy. 10:556–561. 2014.PubMed/NCBI View Article : Google Scholar

4 

Stanković V, Mihailović V, Mitrović S and Jurišić V: Protective and therapeutic possibility of medical herbs for liver cirrhosis. Rom J Morphol Embryol. 58:723–729. 2017.PubMed/NCBI

5 

Walker C, Mojares E and Del Río Hernández A: Role of extracellular matrix in development and cancer progression. Int J Mol Sci. 19(3028)2018.PubMed/NCBI View Article : Google Scholar

6 

Yang Y, Chen XX, Li WX, Wu XQ, Huang C, Xie J, Zhao YX, Meng XM and Li J: EZH2-mediated repression of Dkk1 promotes hepatic stellate cell activation and hepatic fibrosis. J Cell Mol Med. 21:2317–2328. 2017.PubMed/NCBI View Article : Google Scholar

7 

Dong F, Jiang S, Li J, Zhu L, Huang Y, Jiang X, Hu X, Zhou Q, Zhang Z and Bao Z: The histone demethylase KDM4D promotes hepatic fibrogenesis by modulating Toll-like receptor 4 signaling pathway. EBioMedicine. 39:472–483. 2019.PubMed/NCBI View Article : Google Scholar

8 

Raeisossadati R, Móvio MI, Walter LT, Takada SH, Del Debbio CB and Kihara AH: Small molecule GSK-J1 affects differentiation of specific neuronal subtypes in developing rat retina. Mol Neurobiol. 56:1972–1983. 2019.PubMed/NCBI View Article : Google Scholar

9 

Rotili D, Tomassi S, Conte M, Benedetti R, Tortorici M, Ciossani G, Valente S, Marrocco B, Labella D, Novellino E, et al: Pan-histone demethylase inhibitors simultaneously targeting Jumonji C and lysine-specific demethylases display high anticancer activities. J Med Chem. 57:42–55. 2014.PubMed/NCBI View Article : Google Scholar

10 

Mettananda S, Fisher CA, Sloane-Stanley JA, Taylor S, Oppermann U, Gibbons RJ and Higgs DR: Selective silencing of α-globin by the histone demethylase inhibitor IOX1: A potentially new pathway for treatment of β-thalassemia. Haematologica. 102:e80–e84. 2017.PubMed/NCBI View Article : Google Scholar

11 

Hu Q, Chen J, Zhang J, Xu C, Yang S and Jiang H: IOX1, a JMJD2A inhibitor, suppresses the proliferation and migration of vascular smooth muscle cells induced by angiotensin II by regulating the expression of cell cycle-related proteins. Int J Mol Med. 37:189–196. 2016.PubMed/NCBI View Article : Google Scholar

12 

Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001.PubMed/NCBI View Article : Google Scholar

13 

Hernández-Aquino E and Muriel P: Beneficial effects of naringenin in liver diseases: Molecular mechanisms. World J Gastroenterol. 24:1679–1707. 2018.PubMed/NCBI View Article : Google Scholar

14 

Ezhilarasan D, Sokal E and Najimi M: Hepatic fibrosis: It is time to go with hepatic stellate cell-specific therapeutic targets. Hepatobiliary Pancreat Dis Int. 17:192–197. 2018.PubMed/NCBI View Article : Google Scholar

15 

Tsuchida T and Friedman SL: Mechanisms of hepatic stellate cell activation. Nat Rev Gastroenterol Hepatol. 14:397–411. 2017.PubMed/NCBI View Article : Google Scholar

16 

Yoshida K, Matsuzaki K, Murata M, Yamaguchi T, Suwa K and Okazaki K: Clinico-pathological importance of TGF-β/phospho-smad signaling during human hepatic fibrocarcinogenesis. Cancers (Basel). 10(183)2018.PubMed/NCBI View Article : Google Scholar

17 

Kim MS, Cho HI, Yoon HJ, Ahn YH, Park EJ, Jin YH and Jang YK: JIB-04, a small molecule histone demethylase inhibitor, selectively targets colorectal cancer stem cells by inhibiting the Wnt/β-catenin signaling pathway. Sci Rep. 8(6611)2018.PubMed/NCBI View Article : Google Scholar

18 

Hopkinson RJ, Tumber A, Yapp C, Chowdhury R, Aik W, Che KH, Li XS, Kristensen JBL, King ONF, Chan MC, et al: 5-Carboxy-8-hydroxyquinoline is a broad spectrum 2-oxoglutarate oxygenase inhibitor which causes Iron translocation. Chem Sci. 4:3110–3117. 2013.PubMed/NCBI View Article : Google Scholar

19 

Schwabe RF and Luedde T: Apoptosis and necroptosis in the liver: A matter of life and death. Nat Rev Gastroenterol Hepatol. 15:738–752. 2018.PubMed/NCBI View Article : Google Scholar

20 

Liu K, Li X, Cao Y, Ge Y, Wang J and Shi B: miR-132 inhibits cell proliferation, invasion and migration of hepatocellular carcinoma by targeting PIK3R3. Int J Oncol. 47:1585–1593. 2015.PubMed/NCBI View Article : Google Scholar

21 

Sun YY, Li XF, Meng XM, Huang C, Zhang L and Li J: Macrophage phenotype in liver injury and repair. Scand J Immunol. 85:166–174. 2017.PubMed/NCBI View Article : Google Scholar

22 

Koyama Y, Xu J, Liu X and Brenner DA: New developments on the treatment of liver fibrosis. Dig Dis. 34:589–596. 2016.PubMed/NCBI View Article : Google Scholar

23 

Marrone G, Shah VH and Gracia-Sancho J: Sinusoidal communication in liver fibrosis and regeneration. J Hepatol. 65:608–617. 2016.PubMed/NCBI View Article : Google Scholar

24 

Fung E and Tsukamoto H: Morphogen-related therapeutic targets for liver fibrosis. Clin Res Hepatol Gastroenterol. 39 (Suppl 1):S69–S74. 2015.PubMed/NCBI View Article : Google Scholar

25 

Omar R, Yang J, Liu H, Davies NM and Gong Y: Hepatic stellate cells in liver fibrosis and siRNA-based therapy. Rev Physiol Biochem Pharmacol. 172:1–37. 2016.PubMed/NCBI View Article : Google Scholar

26 

Chen PJ, Huang C, Meng XM and Li J: Epigenetic modifications by histone deacetylases: Biological implications and therapeutic potential in liver fibrosis. Biochimie. 116:61–69. 2015.PubMed/NCBI View Article : Google Scholar

27 

Perugorria MJ, Wilson CL, Zeybel M, Walsh M, Amin S, Robinson S, White SA, Burt AD, Oakley F, Tsukamoto H, et al: Histone methyltransferase ASH1 orchestrates fibrogenic gene transcription during myofibroblast transdifferentiation. Hepatology. 56:1129–1139. 2012.PubMed/NCBI View Article : Google Scholar

28 

Irvine KM, Wockner LF, Hoffmann I, Horsfall LU, Fagan KJ, Bijin V, Lee B, Clouston AD, Lampe G, Connolly JE and Powell EE: Multiplex serum protein analysis identifies novel biomarkers of advanced fibrosis in patients with chronic liver disease with the potential to improve diagnostic accuracy of established biomarkers. PLoS One. 11(e0167001)2016.PubMed/NCBI View Article : Google Scholar

29 

Magdaleno F, Arriazu E, Ruiz de Galarreta M, Chen Y, Ge X, Conde de la Rosa L and Nieto N: Cartilage oligomeric matrix protein participates in the pathogenesis of liver fibrosis. J Hepatol. 65:963–971. 2016.PubMed/NCBI View Article : Google Scholar

30 

Wang H, Yang LM and Huang L: Clinical effects of qianggan capsule on the liver tissue pathology and PDGF-BB, TGF-beta1, TIMP-1, and MMP-1 factors in patients with chronic hepatitis B. Zhongguo Zhong Xi Yi Jie He Za Zhi. 31:1337–1340. 2011.PubMed/NCBI(In Chinese).

31 

Yu Y, Li ZQ, Chen K, Zhan P, Liao J and Ruan QY: Significance and expressions of MMP-1, TIMP-1 and TGF-β1 in valve tissue of rheumatic heart disease. Sichuan Da Xue Xue Bao Yi Xue Ban. 48:52–56. 2017.PubMed/NCBI(In Chinese).

32 

Agrinier N, Thilly N, Boivin JM, Dousset B, Alla F and Zannad F: Prognostic value of serum PIIINP, MMP1 and TIMP1 levels in hypertensive patients: A community-based prospective cohort study. Fundam Clin Pharmacol. 27:572–580. 2013.PubMed/NCBI View Article : Google Scholar

33 

Tian T, Zhan W, Xie R, Yu L, Zheng L, Tang L, Liu X, Guo X, Zhang J, Han B, et al: Epigenetic histone methylation regulates MMP-1 expression in myofibroblastichepatic stellate cell. Int J Clin Exp Med. 10:15187–15195. 2017.

34 

Wang Q, Wang LX, Zeng JP, Liu XJ, Liang XM and Zhou YB: Histone demethylase retinoblastoma binding protein 2 regulates the expression of α-smooth muscle actin and vimentin incirrhotic livers. Brazilian J Med Biol Res. 46:739–745. 2013.PubMed/NCBI View Article : Google Scholar

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Copy and paste a formatted citation
Spandidos Publications style
Tian T, Xie R, Ding K, Han B, Yang Q and Yang X: IOX1 protects from TGF‑β induced fibrosis in LX‑2 cells via the regulation of extracellular matrix protein expression. Exp Ther Med 21: 180, 2021.
APA
Tian, T., Xie, R., Ding, K., Han, B., Yang, Q., & Yang, X. (2021). IOX1 protects from TGF‑β induced fibrosis in LX‑2 cells via the regulation of extracellular matrix protein expression. Experimental and Therapeutic Medicine, 21, 180. https://doi.org/10.3892/etm.2021.9611
MLA
Tian, T., Xie, R., Ding, K., Han, B., Yang, Q., Yang, X."IOX1 protects from TGF‑β induced fibrosis in LX‑2 cells via the regulation of extracellular matrix protein expression". Experimental and Therapeutic Medicine 21.3 (2021): 180.
Chicago
Tian, T., Xie, R., Ding, K., Han, B., Yang, Q., Yang, X."IOX1 protects from TGF‑β induced fibrosis in LX‑2 cells via the regulation of extracellular matrix protein expression". Experimental and Therapeutic Medicine 21, no. 3 (2021): 180. https://doi.org/10.3892/etm.2021.9611
Copy and paste a formatted citation
x
Spandidos Publications style
Tian T, Xie R, Ding K, Han B, Yang Q and Yang X: IOX1 protects from TGF‑β induced fibrosis in LX‑2 cells via the regulation of extracellular matrix protein expression. Exp Ther Med 21: 180, 2021.
APA
Tian, T., Xie, R., Ding, K., Han, B., Yang, Q., & Yang, X. (2021). IOX1 protects from TGF‑β induced fibrosis in LX‑2 cells via the regulation of extracellular matrix protein expression. Experimental and Therapeutic Medicine, 21, 180. https://doi.org/10.3892/etm.2021.9611
MLA
Tian, T., Xie, R., Ding, K., Han, B., Yang, Q., Yang, X."IOX1 protects from TGF‑β induced fibrosis in LX‑2 cells via the regulation of extracellular matrix protein expression". Experimental and Therapeutic Medicine 21.3 (2021): 180.
Chicago
Tian, T., Xie, R., Ding, K., Han, B., Yang, Q., Yang, X."IOX1 protects from TGF‑β induced fibrosis in LX‑2 cells via the regulation of extracellular matrix protein expression". Experimental and Therapeutic Medicine 21, no. 3 (2021): 180. https://doi.org/10.3892/etm.2021.9611
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