Journal
JOURNAL OF HEPATOLOGY
Volume 50, Issue 4, Pages 766-778Publisher
ELSEVIER
DOI: 10.1016/j.jhep.2008.11.025
Keywords
Hepatic stellate cells; Activation; miR-16; miR-15b; Gene ontology; Bcl-2; Caspase; Apoptosis
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Funding
- Foundation of Shanghai Commission of Science Technology of Research Program [07JC14044]
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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. (c) 2009 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
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