TSA increases C/EBP‑α expression by increasing its lysine acetylation in hepatic stellate cells

Tao,Li‑Li; Ding,Di; Yin,Wei‑Hua; Peng,Ji‑Ying; Hou,Chen‑Jian; Liu,Xiu‑Ping; Chen,Yao‑Li

doi:10.3892/mmr.2017.7358

November-2017 Volume 16 Issue 5

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November-2017 Volume 16 Issue 5

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Article

TSA increases C/EBP‑α expression by increasing its lysine acetylation in hepatic stellate cells

Authors:
- Li‑Li Tao
- Di Ding
- Wei‑Hua Yin
- Ji‑Ying Peng
- Chen‑Jian Hou
- Xiu‑Ping Liu
- Yao‑Li Chen
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Affiliations: Department of Pathology, Peking University, Shenzhen Hospital, Shenzhen, Guangdong 518001, P.R. China, Department of Pathology, Fudan University Affiliated Zhongshan Hospital, Shanghai 200032, P.R. China, Department of Pathology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, P.R. China
Pages: 6088-6093
|
Published online on: August 24, 2017

https://doi.org/10.3892/mmr.2017.7358
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Abstract

CCAAT enhancer binding protein‑α (C/EBP‑α) is a transcription factor expressed only in certain tissues, including the liver. It has been previously demonstrated that C/EBP‑α may induce apoptosis in hepatic stellate cells (HSCs), raising the question of whether acetylation of C/EBP‑α is associated with HSCs, and the potential associated mechanism. A total of three histone deacetylase inhibitors (HDACIs), including trichostatin A (TSA), suberoylanilide hydroxamic acid and nicotinamide, were selected to determine whether acetylation affects C/EBP‑α expression. A Cell Counting Kit‑8 assay was used to determine the rate of proliferation inhibition following treatment with varying doses of the three HDACIs in HSC‑T6 and BRL‑3A cells. Western blot analysis was used to examine Caspase‑3, ‑8, ‑9, and ‑12 levels in HSC‑T6 cells treated with adenoviral‑C/EBP‑α and/or TSA. Following treatment with TSA, a combination of reverse transcription‑quantitative polymerase chain reaction and western blot analyses was used to determine the inherent C/EBP‑α mRNA and protein levels in HSC‑T6 cells at 0, 1, 2, 4, 8, 12, 24, 36 and 48 h. Nuclear and cytoplasmic proteins were extracted to examine C/EBP‑α distribution. Co‑immunoprecipitation analysis was used to examine the lysine acetylation of C/EBP‑α. It was observed that TSA inhibited the proliferation of HSC‑T6 cells to a greater extent compared with BRL‑3A cells, following treatment with the three HDACIs. TSA induced apoptosis in HSC‑T6 cells and enhanced the expression of C/EBP‑α. Following treatment of HSC‑T6 cells with TSA, inherent C/EBP‑α expression increased in a time‑dependent manner, and its lysine acetylation simultaneously increased. Therefore, the results of the present study suggested that TSA may increase C/EBP‑α expression by increasing its lysine acetylation in HSCs.

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1	Reeves HL and Friedman SL: Activation of hepatic stellate cells-A key issue in liver fibrosis. Front Biosci. 7:d808–d826. 2002. View Article : Google Scholar : PubMed/NCBI
2	Mueller BU and Pabst T: C/EBP alpha and the pathophysiology of acute myeloid leukemia. Curr Opin Hematol. 13:7–14. 2006. View Article : Google Scholar : PubMed/NCBI
3	Lane MD, Tang QQ and Jiang MS: Role of the CCAAT enhancer binding proteins (C/EBPs) in adipocyte differentiation. Biochem Biophys Res Commun. 266:677–683. 1999. View Article : Google Scholar : PubMed/NCBI
4	Wang X, Huang G, Mei S, Qian J, Ji J and Zhang J: Over-expression of C/EBP-alpha induces apoptosis in cultured rat hepatic stellate cells depending on p53 and peroxisome proliferator-activated receptor-gamma. Biochem Biophys Res Commun. 380:286–291. 2009. View Article : Google Scholar : PubMed/NCBI
5	Mei S, Wang X, Zhang J, Qian J and Ji JL: In vivo transfection of C/EBP-alpha gene could ameliorate CCL(4)-induced hepatic fibrosis in mice. Hepatol Res. 37:531–539. 2007. View Article : Google Scholar : PubMed/NCBI
6	Tao LL, Cheng YY, Ding D, Mei S, Xu JW, Yu J, Ou-Yang Q, Deng L, Chen Q, Li QQ, et al: C/EBP-α ameliorates CCl(4)-induced liver fibrosis in mice through promoting apoptosis of hepatic stellate cells with little apoptotic effect on hepatocytes in vitro and in vivo. Apoptosis. 17:492–502. 2012. View Article : Google Scholar : PubMed/NCBI
7	Tada Y, Brena RM, Hackanson B, Morrison C, Otterson GA and Plass C.: Epigenetic modulation of tumor suppressor CCAAT/Enhancer binding protein a activity in lung cancer. J Natl Cancer Inst. 98:396–406. 2006. View Article : Google Scholar : PubMed/NCBI
8	Hackanson B, Bennett KL, Brena RM, Jiang J, Claus R, Chen SS, Blagitko-Dorfs N, Maharry K, Whitman SP, Schmittgen TD, et al: Epigenetic modification of CCAAT/enhancer binding protein alpha expression in acute myeloid leukemia. Cancer Res. 68:3142–3151. 2008. View Article : Google Scholar : PubMed/NCBI
9	Bennett KL, Hackanson B, Smith LT, Morrison CD, Lang JC, Schuller DE, Weber F, Eng C and Plass C: Tumor suppressor activity of CCAAT/enhancer binding protein alpha is epigenetically down-regulated in head and neck squamous cell carcinoma. Cancer Res. 67:4657–4664. 2007. View Article : Google Scholar : PubMed/NCBI
10	Kumagai T, Akagi T, Desmond JC, Kawamata N, Gery S, Imai Y, Song JH, Gui D, Said J and Koeffler HP: Epigenetic regulation and molecular characterization of C/EBP alpha in pancreatic cancer cells. Int J Cancer. 124:827–833. 2009. View Article : Google Scholar : PubMed/NCBI
11	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. View Article : Google Scholar : PubMed/NCBI
12	Gridelli C, Rossi A and Maione P: The potential role of histone deacetylase inhibitors in the treatment of non-small-cell lung cancer. Crit Rev Oncol Hematol. 68:29–36. 2008. View Article : Google Scholar : PubMed/NCBI
13	Niki T, Rombouts K, De Bleser P, De Smet K, Rogiers V, Schuppan D, Yoshida M, Gabbiani G and Geerts A: A histone deacetylase inhibitor, trichostatin A, suppresses myofibroblastic differentiation of rat hepatic stellate cells in primary culture. Hepatology. 29:858–867. 1999. View Article : Google Scholar : PubMed/NCBI
14	Yang XJ and Seto E: Lysine acetylation: Codified crosstalk with other posttranslational modifications. Mol Cell. 31:449–461. 2008. View Article : Google Scholar : PubMed/NCBI
15	Glozak MA, Sengupta N, Zhang X and Seto E: Acetylation and deacetylation of non-histone proteins. Gene. 363:15–23. 2005. View Article : Google Scholar : PubMed/NCBI

Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

TSA increases C/EBP‑α expression by increasing its lysine acetylation in hepatic stellate cells

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