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DNMT1 controls LncRNA H19/ERK signal pathway in hepatic stellate cell activation and fibrosis.
Toxicol Lett. 2018 Oct 01; 295:325-334.TL

Abstract

Hepatic stellate cells (HSCs) activation is considered as a pivotal event in liver fibrosis. In HSCs activation and fibrosis, epigenetic events are important. Although HSCs activation alters DNA methylation, it is unknown, whether it also affects other epigenetic processes, including LncRNA and its recognition. The aim of this study was to identify the mechanism of DNA methyltransferase 1 (DNMT1) expression and its role in regulating LncRNA H19 during HSCs activation and fibrosis. Expression of DNMT1 and LncRNA H19 were determined in activated HSCs and CCl4-induced rat liver fibrosis tissue. The relationship between the LncRNA H19 and DNMT1 expression was examined in vitro. LncRNA H19 expression was reduced in activated HSCs and rat liver fibrosis tissue, whereas DNMT1 expression and methylation of the LncRNA H19 promoter were increased. Treatment of HSCs of DNMT1-siRNA blocked cell proliferation. Knockdown of DNMT1 elevated H19 expression in activated HSCs, and over-expression of DNMT1 inhibited H19 expression in activated HSCs. Moreover, we investigated the effect of H19 on ERK signal pathway. Treatment HSCs with H19-siRNA increased the expression of p-ERK1/2 in HSCs. Treatment with 5'-aza-2'-deoxycytidine in activated HSCs model reduced fibrosis gene and DNMT1 expression, enhanced H19 expression, and attenuated HSCs activation. These data connect HSCs activation with a DNMT1-LncRNA H19 epigenetic pathway that is important for liver fibrosis.

Authors+Show Affiliations

Department of Pharmacology and Institute of Natural Medicine, Anhui Medical University, Hefei, 230032, China; Department of Pharmacology, The Second Hospital of Anhui Medical University, Hefei, 230601, China.Department of Pharmacology and Institute of Natural Medicine, Anhui Medical University, Hefei, 230032, China.Department of Pharmacology and Institute of Natural Medicine, Anhui Medical University, Hefei, 230032, China. Electronic address: yncs08@126.com.Department of Cardiothoracic Surgery, The Second Hospital of Anhui Medical University, Hefei, 230601, China.School of Pharmacy, Anhui Medical University, Hefei, 230032, China. Electronic address: yncs01@hotmail.com.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

30010033

Citation

Yang, Jing-Jing, et al. "DNMT1 Controls LncRNA H19/ERK Signal Pathway in Hepatic Stellate Cell Activation and Fibrosis." Toxicology Letters, vol. 295, 2018, pp. 325-334.
Yang JJ, She Q, Yang Y, et al. DNMT1 controls LncRNA H19/ERK signal pathway in hepatic stellate cell activation and fibrosis. Toxicol Lett. 2018;295:325-334.
Yang, J. J., She, Q., Yang, Y., Tao, H., & Li, J. (2018). DNMT1 controls LncRNA H19/ERK signal pathway in hepatic stellate cell activation and fibrosis. Toxicology Letters, 295, 325-334. https://doi.org/10.1016/j.toxlet.2018.07.013
Yang JJ, et al. DNMT1 Controls LncRNA H19/ERK Signal Pathway in Hepatic Stellate Cell Activation and Fibrosis. Toxicol Lett. 2018 Oct 1;295:325-334. PubMed PMID: 30010033.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - DNMT1 controls LncRNA H19/ERK signal pathway in hepatic stellate cell activation and fibrosis. AU - Yang,Jing-Jing, AU - She,Qian, AU - Yang,Yan, AU - Tao,Hui, AU - Li,Jun, Y1 - 2018/07/20/ PY - 2018/04/18/received PY - 2018/07/06/revised PY - 2018/07/11/accepted PY - 2018/7/17/pubmed PY - 2018/8/30/medline PY - 2018/7/17/entrez KW - Carbon tetrachloride KW - DNA methylation KW - Hepatic stellate cells activation KW - Liver fibrosis KW - LncRNA H19 SP - 325 EP - 334 JF - Toxicology letters JO - Toxicol. Lett. VL - 295 N2 - Hepatic stellate cells (HSCs) activation is considered as a pivotal event in liver fibrosis. In HSCs activation and fibrosis, epigenetic events are important. Although HSCs activation alters DNA methylation, it is unknown, whether it also affects other epigenetic processes, including LncRNA and its recognition. The aim of this study was to identify the mechanism of DNA methyltransferase 1 (DNMT1) expression and its role in regulating LncRNA H19 during HSCs activation and fibrosis. Expression of DNMT1 and LncRNA H19 were determined in activated HSCs and CCl4-induced rat liver fibrosis tissue. The relationship between the LncRNA H19 and DNMT1 expression was examined in vitro. LncRNA H19 expression was reduced in activated HSCs and rat liver fibrosis tissue, whereas DNMT1 expression and methylation of the LncRNA H19 promoter were increased. Treatment of HSCs of DNMT1-siRNA blocked cell proliferation. Knockdown of DNMT1 elevated H19 expression in activated HSCs, and over-expression of DNMT1 inhibited H19 expression in activated HSCs. Moreover, we investigated the effect of H19 on ERK signal pathway. Treatment HSCs with H19-siRNA increased the expression of p-ERK1/2 in HSCs. Treatment with 5'-aza-2'-deoxycytidine in activated HSCs model reduced fibrosis gene and DNMT1 expression, enhanced H19 expression, and attenuated HSCs activation. These data connect HSCs activation with a DNMT1-LncRNA H19 epigenetic pathway that is important for liver fibrosis. SN - 1879-3169 UR - https://www.unboundmedicine.com/medline/citation/30010033/DNMT1_controls_LncRNA_H19/ERK_signal_pathway_in_hepatic_stellate_cell_activation_and_fibrosis_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0378-4274(18)31498-X DB - PRIME DP - Unbound Medicine ER -