miR-15b and miR-16 regulate TNF mediated hepatocyte apoptosis via BCL2 in acute liver failure

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...

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Bibliographic Details
Published in:Apoptosis (London) 2012-07, Vol.17 (7), p.702-716
Main Authors: An, Fangmei, Gong, Bangdong, Wang, Hui, Yu, Dongshan, Zhao, Gangde, Lin, Lanyi, Tang, Weiliang, Yu, Hong, Bao, Shisan, Xie, Qing
Format: Article
Language:English
Subjects:
3' Untranslated Regions - genetics
Animals
Apoptosis - genetics
Base Sequence
Biochemistry
Bioinformatics
Biomedical and Life Sciences
Biomedicine
Cancer Research
Cell Biology
Computational Biology
Down-Regulation - genetics
Flow Cytometry
Gene Expression Profiling
Gene Knockdown Techniques
Hepatocytes - metabolism
Hepatocytes - pathology
Histopathology
Immunohistochemistry
Inflammation Mediators - metabolism
Liver - metabolism
Liver - pathology
Liver Failure, Acute - genetics
Liver Failure, Acute - pathology
Male
Mice
Mice, Inbred BALB C
MicroRNAs - genetics
MicroRNAs - metabolism
Molecular Sequence Data
Oligonucleotide Array Sequence Analysis
Oncology
Original Paper
Proto-Oncogene Proteins c-bcl-2 - genetics
Proto-Oncogene Proteins c-bcl-2 - metabolism
RNA, Messenger - genetics
RNA, Messenger - metabolism
Tumor Necrosis Factor-alpha - biosynthesis
Tumor Necrosis Factor-alpha - metabolism
Up-Regulation - genetics
Virology
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Summary: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  
ISSN:1360-8185
1573-675X
DOI:10.1007/s10495-012-0704-7