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World J Gastroenterol. 2011 Jun 14;17(22):2748-73. doi: 10.3748/wjg.v17.i22..

miRNA studies in in vitro and in vivo activated hepatic stellate cells.

Author information

  • 1Institute of Bioengineering and Nanotechnology, 31 Biopolis Way, The Nanos #04-01, Singapore 138669, Singapore.

Abstract

AIM:

To understand which and how different miRNAs are implicated in the process of hepatic stellate cell (HSC) activation.

METHODS:

We used microarrays to examine the differential expression of miRNAs during in vitro activation of primary HSCs (pHSCs). The transcriptome changes upon stable transfection of rno-miR-146a into an HSC cell line were studied using cDNA microarrays. Selected differentially regulated miRNAs were investigated by quantitative real-time polymerase chain reaction during in vivo HSC activation. The effect of miRNA mimics and inhibitor on the in vitro activation of pHSCs was also evaluated.

RESULTS:

We found that 16 miRNAs were upregulated and 26 were downregulated significantly in 10-d in vitro activated pHSCs in comparison to quiescent pHSCs. Overexpression of rno-miR-146a was characterized by marked upregulation of tissue inhibitor of metalloproteinase-3, which is implicated in the regulation of tumor necrosis factor-α activity. Differences in the regulation of selected miRNAs were observed comparing in vitro and in vivo HSC activation. Treatment with miR-26a and 29a mimics, and miR-214 inhibitor during in vitro activation of pHSCs induced significant downregulation of collagen type I transcription.

CONCLUSION:

Our results emphasize the different regulation of miRNAs in in vitro and in vivo activated pHSCs. We also showed that miR-26a, 29a and 214 are involved in the regulation of collagen type I mRNA.

KEYWORDS:

Hepatic stellate cells; Nuclear factor-κB; miR-146a; miRNA

PMID:
21734783
[PubMed - indexed for MEDLINE]
PMCID:
PMC3122263
Free PMC Article

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