miR-15b and miR-16 regulate TNF mediated hepatocyte apoptosis via BCL2 in acute liver failure
| Autor: | Lanyi Lin, Dongshan Yu, Shisan Bao, Qing Xie, Hong Yu, Hui Wang, Gangde Zhao, Bang-dong Gong, Fangmei An, Weiliang Tang |
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| Rok vydání: | 2012 |
| Předmět: |
Male
Cancer Research Microarray Clinical Biochemistry Molecular Sequence Data Pharmaceutical Science Down-Regulation Apoptosis Biology Flow cytometry Mice microRNA medicine Animals RNA Messenger Gene 3' Untranslated Regions Oligonucleotide Array Sequence Analysis Pharmacology Mice Inbred BALB C medicine.diagnostic_test Base Sequence Tumor Necrosis Factor-alpha Gene Expression Profiling digestive oral and skin physiology Biochemistry (medical) Computational Biology Cell Biology Liver Failure Acute Flow Cytometry Immunohistochemistry In vitro Up-Regulation Gene expression profiling MicroRNAs Liver Proto-Oncogene Proteins c-bcl-2 Gene Knockdown Techniques Immunology Cancer research Hepatocytes Tumor necrosis factor alpha Inflammation Mediators |
| Zdroj: | Apoptosis : an international journal on programmed cell death. 17(7) |
| ISSN: | 1573-675X |
| Popis: | Acute liver failure (ALF) still has an unacceptable high mortality rate, despite substantial improvements with multidisciplinary care. The precise underlying mechanism of ALF remains to be explored. It has been reported that microRNAs (miRNAs) are novel regulators in a number of liver diseases, but the role of miRNAs in the development of ALF is not fully understood. An ALF murine model was generated by ip injection of d-GalN/LPS, which was confirmed with histopathology and biochemistry. The hepatic miRNA expression profile in ALF was determined by microarray and verified by qRT-PCR. The functions and signal pathways of the targeted genes of these deregulated miRNAs were predicted, using bioinformatics analysis. The possible underlying mechanism was investigated by exploring the relationship between miRNA modification and hepatocyte apoptosis. There were a total of 95 significantly changed miRNAs in ALF compared to mock-treated (P < 0.01). Among these 95 miRNAs, 20 were up-regulated and 26 were down-regulated at both 5 and 7 h time points. Bioinformatics analysis predicted that some of these 46 miRNAs were involved in apoptosis. Among the up-regulated miRNAs involved in apoptosis, miR-15b and miR-16 showed the highest enrichment and targeted the common anti-apoptotic gene, BCL2. Our in vitro data demonstrated that miR-15b and/or miR-16 regulated BCL2 at the protein level. Inhibition of miR-15b and/or miR-16 reduced hepatic apoptosis and TNF production. These data suggest that miR-15b and miR-16 regulate TNF mediated hepatic apoptosis via BCL2 during ALF, and may shed light on the development of a therapeutic strategy for treatment of ALF. |
| Databáze: | OpenAIRE |
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