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J Hepatol. 2009 Apr;50(4):766-78. doi: 10.1016/j.jhep.2008.11.025. Epub 2009 Feb 2.

miR-15b and miR-16 are implicated in activation of the rat hepatic stellate cell: An essential role for apoptosis.

Author information

1
Digestive Disease Laboratory and Department of Gastroenterology, School of Medicine, Shanghai Jiaotong University, Xinhua Hospital, No. 1665 Kongjiang Road, Shanghai 200092, China.

Abstract

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.

PMID:
19232449
DOI:
10.1016/j.jhep.2008.11.025
[Indexed for MEDLINE]

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