Document Detail


miR-15b and miR-16 are implicated in activation of the rat hepatic stellate cell: An essential role for apoptosis.
MedLine Citation:
PMID:  19232449     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND/AIMS: To reveal the microRNA (miRNA) expression profile and related roles in rat HSCs during activation.
METHODS: miRNA expression profiling was analyzed in quiescent and in culture-activated HSCs by microarray. The differentially expressed miRNAs, as verified by RT-PCR, were subjected to gene ontology (GO) analysis. Furthermore, the effects of miR-16 and miR-15b on the apoptosis of activated HSCs were investigated by Hoechst 33258, TUNEL staining and annexin-V/PI labeling flow cytometry. The underlying mechanism related to Bcl-2 and caspases was assessed.
RESULTS: The upregulated and downregulated miRNAs in activated HSCs were 12 miRNAs and 9 miRNAs, respectively. The differential expression of miR-16, -15b, -122, -138, -143, and -140 was validated. High-enrichment GOs containing apoptosis-related targeted genes and miRNA-gene networks characterized by Bcl-2, which was targeted by the miR-15/16 family, uncovered the critical role of miR-16 and miR-15b in apoptosis. Restoring the intracellular miRNAs by miR-16 and miR-15b administration greatly reduced Bcl-2, and increased the expression of caspases 3, 8, and 9. Significantly elevated rates of apoptosis were then induced in activated HSCs.
CONCLUSIONS: The activation of HSCs relate to 21 miRNAs. Among these, mir-15b and miR-16 may be essential for apoptosis by targeting Bcl-2 and the caspase signaling pathway.
Authors:
Can-Jie Guo; Qin Pan; Ding-Guo Li; Hua Sun; Bo-Wei Liu
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-02-02
Journal Detail:
Title:  Journal of hepatology     Volume:  50     ISSN:  1600-0641     ISO Abbreviation:  J. Hepatol.     Publication Date:  2009 Apr 
Date Detail:
Created Date:  2009-03-16     Completed Date:  2009-07-29     Revised Date:  2012-08-24    
Medline Journal Info:
Nlm Unique ID:  8503886     Medline TA:  J Hepatol     Country:  England    
Other Details:
Languages:  eng     Pagination:  766-78     Citation Subset:  IM    
Affiliation:
Digestive Disease Laboratory and Department of Gastroenterology, School of Medicine, Shanghai Jiaotong University, Xinhua Hospital, No. 1665 Kongjiang Road, Shanghai 200092, China.
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MeSH Terms
Descriptor/Qualifier:
Actins / genetics
Animals
Apoptosis / physiology*
DNA Primers
Desmin / genetics
Down-Regulation
Flow Cytometry
Hepatic Stellate Cells / cytology,  physiology*
In Situ Nick-End Labeling
Male
MicroRNAs / genetics*
Microarray Analysis
Rats
Rats, Sprague-Dawley
Reverse Transcriptase Polymerase Chain Reaction
Up-Regulation
Chemical
Reg. No./Substance:
0/Actins; 0/DNA Primers; 0/Desmin; 0/MicroRNAs; 0/smooth muscle actin, rat

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