Activation of TAF9 Danshensu-Induced Upregulation of HDAC1 Expression Alleviates Non-alcoholic Fatty Liver Disease

Overview

Journal Front Pharmacol

Date 2021 Dec 20

PMID 34925033

Citations 1

Authors

Ruiwen Wang

Zhecheng Wang

Ruimin Sun

Rong Fu

Yu Sun

Meiyang Zhu

Yunfei Geng

Dongyan Gao

Xiaofeng Tian

Yan Zhao

Jihong Yao

Affiliations

Soon will be listed here.

Abstract

Fatty acid -oxidation is an essential pathogenic mechanism in nonalcoholic fatty liver disease (NAFLD), and TATA-box binding protein associated factor 9 (TAF9) has been reported to be involved in the regulation of fatty acid -oxidation. However, the function of TAF9 in NAFLD, as well as the mechanism by which TAF9 is regulated, remains unclear. In this study, we aimed to investigate the signaling mechanism underlying the involvement of TAF9 in NAFLD and the protective effect of the natural phenolic compound Danshensu (DSS) against NAFLD via the HDAC1/TAF9 pathway. An model of high-fat diet (HFD)-induced NAFLD and a palmitic acid (PA)-treated AML-12 cell model were developed. Pharmacological treatment with DSS significantly increased fatty acid -oxidation and reduced lipid droplet (LD) accumulation in NAFLD. TAF9 overexpression had the same effects on these processes both and . Interestingly, the protective effect of DSS was markedly blocked by TAF9 knockdown. Mechanistically, TAF9 was shown to be deacetylated by HDAC1, which regulates the capacity of TAF9 to mediate fatty acid -oxidation and LD accumulation during NAFLD. In conclusion, TAF9 is a key regulator in the treatment of NAFLD that acts by increasing fatty acid -oxidation and reducing LD accumulation, and DSS confers protection against NAFLD through the HDAC1/TAF9 pathway.

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References

Xu P, Hong F, Wang J, Wang J, Zhao X, Wang S . DBZ is a putative PPARγ agonist that prevents high fat diet-induced obesity, insulin resistance and gut dysbiosis. Biochim Biophys Acta Gen Subj. 2017; 1861(11 Pt A):2690-2701. DOI: 10.1016/j.bbagen.2017.07.013. View

Yang X, Seto E . HATs and HDACs: from structure, function and regulation to novel strategies for therapy and prevention. Oncogene. 2007; 26(37):5310-8. DOI: 10.1038/sj.onc.1210599. View

Draney C, Austin M, Leifer A, Smith C, Kener K, Aitken T . HDAC1 overexpression enhances β-cell proliferation by down-regulating Cdkn1b/p27. Biochem J. 2018; 475(24):3997-4010. DOI: 10.1042/BCJ20180465. View

Wanders R, Komen J, Kemp S . Fatty acid omega-oxidation as a rescue pathway for fatty acid oxidation disorders in humans. FEBS J. 2010; 278(2):182-94. DOI: 10.1111/j.1742-4658.2010.07947.x. View

Estes C, Razavi H, Loomba R, Younossi Z, Sanyal A . Modeling the epidemic of nonalcoholic fatty liver disease demonstrates an exponential increase in burden of disease. Hepatology. 2017; 67(1):123-133. PMC: 5767767. DOI: 10.1002/hep.29466. View

Qian Y, Liu Z, Yan H, Yuan Y, Levenson A, Li K . Pterostilbene inhibits MTA1/HDAC1 complex leading to PTEN acetylation in hepatocellular carcinoma. Biomed Pharmacother. 2018; 101:852-859. DOI: 10.1016/j.biopha.2018.03.022. View

Schulze R, McNiven M . Lipid Droplet Formation and Lipophagy in Fatty Liver Disease. Semin Liver Dis. 2019; 39(3):283-290. PMC: 8718013. DOI: 10.1055/s-0039-1685524. View

Xie G, Yu Z, Jia D, Jiao R, Deng W . E(y)1/TAF9 mediates the transcriptional output of Notch signaling in Drosophila. J Cell Sci. 2014; 127(Pt 17):3830-9. PMC: 4150066. DOI: 10.1242/jcs.154583. View

Yang L, Roh Y, Song J, Zhang B, Liu C, Loomba R . Transforming growth factor beta signaling in hepatocytes participates in steatohepatitis through regulation of cell death and lipid metabolism in mice. Hepatology. 2013; 59(2):483-95. PMC: 3946696. DOI: 10.1002/hep.26698. View

10.

Zeng P, Wang Y, Zheng Y, Song X, Yin Y . Cancer‑testis antigen HCA587/MAGEC2 interacts with the general transcription coactivator TAF9 in cancer cells. Mol Med Rep. 2017; 17(2):3226-3231. DOI: 10.3892/mmr.2017.8260. View

11.

Farrell G, Larter C . Nonalcoholic fatty liver disease: from steatosis to cirrhosis. Hepatology. 2006; 43(2 Suppl 1):S99-S112. DOI: 10.1002/hep.20973. View

12.

Yamauchi M, Sricholpech M . Lysine post-translational modifications of collagen. Essays Biochem. 2012; 52:113-33. PMC: 3499978. DOI: 10.1042/bse0520113. View

13.

Li L, Chen L, Hu L, Liu Y, Sun H, Tang J . Nuclear factor high-mobility group box1 mediating the activation of Toll-like receptor 4 signaling in hepatocytes in the early stage of nonalcoholic fatty liver disease in mice. Hepatology. 2011; 54(5):1620-30. DOI: 10.1002/hep.24552. View

14.

Bieniossek C, Papai G, Schaffitzel C, Garzoni F, Chaillet M, Scheer E . The architecture of human general transcription factor TFIID core complex. Nature. 2013; 493(7434):699-702. DOI: 10.1038/nature11791. View

15.

Muller M . Hepatic energy and substrate metabolism: a possible metabolic basis for early nutritional support in cirrhotic patients. Nutrition. 1998; 14(1):30-8. DOI: 10.1016/s0899-9007(97)00390-0. View

16.

Soldatov A, Nabirochkina E, Georgieva S, Belenkaja T, Georgiev P . TAFII40 protein is encoded by the e(y)1 gene: biological consequences of mutations. Mol Cell Biol. 1999; 19(5):3769-78. PMC: 84205. DOI: 10.1128/MCB.19.5.3769. View

17.

Rogge M . The role of impaired mitochondrial lipid oxidation in obesity. Biol Res Nurs. 2009; 10(4):356-73. DOI: 10.1177/1099800408329408. View

18.

Black J, Van Rechem C, Whetstine J . Histone lysine methylation dynamics: establishment, regulation, and biological impact. Mol Cell. 2012; 48(4):491-507. PMC: 3861058. DOI: 10.1016/j.molcel.2012.11.006. View

19.

Cao G, Zhu R, Jiang T, Tang D, Kwan H, Su T . Danshensu, a novel indoleamine 2,3-dioxygenase1 inhibitor, exerts anti-hepatic fibrosis effects via inhibition of JAK2-STAT3 signaling. Phytomedicine. 2019; 63:153055. DOI: 10.1016/j.phymed.2019.153055. View

20.

Jian W, Yan B, Huang S, Qiu Y . Histone deacetylase 1 activates PU.1 gene transcription through regulating TAF9 deacetylation and transcription factor IID assembly. FASEB J. 2017; 31(9):4104-4116. PMC: 5572695. DOI: 10.1096/fj.201700022R. View