| Epigenetic regulation of miR-34a expression in alcoholic liver injury. | |
| | |
MedLine Citation:
|
PMID: 22841474 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
Epigenetic changes are associated with the regulation of transcription of key cell regulatory genes [micro RNAs (miRNAs)] during different types of liver injury. This study evaluated the role of methylation-associated miRNA, miR-34a, in alcoholic liver diseases. We identified that ethanol feeding for 4 weeks significantly up-regulated 0.8% of known miRNA compared with controls, including miR-34a. Treatment of normal human hepatocytes (N-Heps) and cholangiocytes [human intrahepatic biliary epithelial cells (HiBECs)] with ethanol and lipopolysaccharide induced a significant increase of miR-34a expression. Overexpression of miR-34a decreased ethanol-induced apoptosis in both N-Heps and HiBECs. In support of the concept that the 5'-promoter region of miR-34a was noted to be embedded within a CpG island, the expression level of miR-34a was significantly increased after demethylation treatment in N-Heps and HiBECs. By methylation-specific PCR, we confirmed that miR-34a activation is associated with ethanol-linked hypomethylation of the miR-34a promoter. A combination of bioinformatics, dual-luciferase reporter assay, mass spectrometry, and Western blot analysis revealed that caspase-2 and sirtuin 1 are the direct targets of miR-34a. Furthermore, modulation of miR-34a also altered expression of matrix metalloproteases 1 and 2, the mediators involved in hepatic remodeling during alcoholic liver fibrosis. These findings provide the basis for an exciting field in which the epigenomic microRNAs of hepatic cells may be manipulated with potential therapeutic benefits in human alcoholic liver diseases. |
| | |
Authors:
|
Fanyin Meng; Shannon S Glaser; Heather Francis; Fuquan Yang; Yuyan Han; Allison Stokes; Dustin Staloch; Jennifer McCarra; Jingang Liu; Julie Venter; Haiying Zhao; Xiuping Liu; Taylor Francis; Scott Swendsen; Chang-Gong Liu; Hidekazu Tsukamoto; Gianfranco Alpini |
Related Documents
:
|
2940084 - Adenovirus stimulation of transcription by rna polymerase iii: evidence for an e1a-depe... 10322454 - Histone deacetylases: transcriptional repression with siners and nurds. 9489704 - Fact, a factor that facilitates transcript elongation through nucleosomes. 22761424 - Polycyclic aromatic hydrocarbons (pahs) mediate transcriptional activation of the atp b... 12007834 - Modified gfap promoter auto-regulates tet-activator expression for increased transactiv... 10889064 - Retinoid signalling and hindbrain patterning. |
Publication Detail:
|
Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2012-07-25 |
Journal Detail:
|
Title: The American journal of pathology Volume: 181 ISSN: 1525-2191 ISO Abbreviation: Am. J. Pathol. Publication Date: 2012 Sep |
Date Detail:
|
Created Date: 2012-08-20 Completed Date: 2012-11-08 Revised Date: 2013-04-18 |
Medline Journal Info:
|
Nlm Unique ID: 0370502 Medline TA: Am J Pathol Country: United States |
Other Details:
|
Languages: eng Pagination: 804-17 Citation Subset: AIM; IM |
Copyright Information:
|
Copyright © 2012 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved. |
Affiliation:
|
Department of Medicine, Scott & White Digestive Disease Research Center, Texas A&M Health Science Center College of Medicine, Temple, USA. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Animals Base Sequence Caspase 2 / metabolism Cell Line Cell Movement / genetics Cell Survival / genetics Cell Transformation, Neoplastic DNA (Cytosine-5-)-Methyltransferase / metabolism DNA Methylation / genetics Disease Models, Animal Epigenesis, Genetic* Ethanol Fatty Liver / genetics, pathology Gene Silencing Humans Liver / metabolism, pathology Liver Diseases, Alcoholic / enzymology, genetics*, pathology Matrix Metalloproteinases / genetics, metabolism Mice Mice, Inbred C57BL MicroRNAs / genetics*, metabolism Molecular Sequence Data Polymerase Chain Reaction Sirtuin 1 / genetics, metabolism |
| Grant Support | |
ID/Acronym/Agency:
|
DK76898/DK/NIDDK NIH HHS; P50AA011999/AA/NIAAA NIH HHS; R01-DK081442/DK/NIDDK NIH HHS; R01DK054811/DK/NIDDK NIH HHS; U01 AA018663/AA/NIAAA NIH HHS |
| Chemical | |
Reg. No./Substance:
|
0/MIRN34 microRNA, human; 0/MIRN34 microRNA, mouse; 0/MicroRNAs; 64-17-5/Ethanol; EC 2.1.1.37/DNA (Cytosine-5-)-Methyltransferase; EC 2.1.1.37/DNA methyltransferase 3B; EC 3.4.22.-/Caspase 2; EC 3.4.24.-/Matrix Metalloproteinases; EC 3.5.1.-/Sirtuin 1 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Transient reduction and activation of circulating dendritic cells in patients with acute myocardial ...
Next Document: Clinicopathologic and radiologic correlation of ossifying fibroma and juvenile ossifying fibroma-an ...