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Published on: October 23, 2018
Suppression of hepatic stellate cell activation by microRNA-29b
Yumiko Sekiya1, Tomohiro Ogawa, Katsutoshi Yoshizato
1Department of Hepatology, Graduate School of Medicine, Osaka City University, Osaka, Japan.
Abstract:
MicroRNAs (miRNAs) participate in the regulation of cellular functions including proliferation, apoptosis, and migration. It has been previously shown that the miR-29 family is involved in regulating type I collagen expression by interacting with the 3'UTR of its mRNA. Here, we investigated the roles of miR-29b in the activation of mouse primary-cultured hepatic stellate cells (HSCs), a principal collagen-producing cell in the liver. Expression of miR-29b was found to be down-regulated during HSC activation in primary culture. Transfection of a miR-29b precursor markedly attenuated the expression of Col1a1 and Col1a2 mRNAs and additionally blunted the increased expression of α-SMA, DDR2, FN1, ITGB1, and PDGFR-β, which are key genes involved in the activation of HSCs. Further, overexpression of miR-29b led HSCs to remain in a quiescent state, as evidenced by their quiescent star-like cell morphology. Although phosphorylation of FAK, ERK, and Akt, and the mRNA expression of c-jun was unaffected, miR-29b overexpression suppressed the expression of c-fos mRNA. These results suggested that miR-29b is involved in the activation of HSCs and could be a candidate molecule for suppressing their activation and consequent liver fibrosis.
Insights
MicroRNAs (miRNAs), specifically miR-29b, are crucial in regulating liver fibrosis by controlling hepatic stellate cell activation. Down-regulation of miR-29b promotes this activation, suggesting miR-29b as a therapeutic target.
Area of Science:
- Molecular Biology
- Cell Biology
- Hepatology
Background:
- MicroRNAs (miRNAs) regulate cellular functions like proliferation and apoptosis.
- The miR-29 family interacts with type I collagen mRNA, influencing its expression.
- Hepatic stellate cells (HSCs) are key collagen-producing cells in the liver, central to liver fibrosis.
Purpose of the Study:
- To investigate the role of miR-29b in the activation of primary-cultured mouse hepatic stellate cells (HSCs).
- To determine if miR-29b can modulate HSC activation and potentially impact liver fibrosis.
Main Methods:
- Primary mouse HSCs were cultured and treated with miR-29b precursors or overexpressed miR-29b.
- Quantitative real-time PCR was used to measure mRNA expression levels of collagen (Col1a1, Col1a2) and activation markers (α-SMA, DDR2, FN1, ITGB1, PDGFR-β, c-fos).
- Cell morphology and signaling pathway components (FAK, ERK, Akt phosphorylation) were assessed.
Main Results:
- miR-29b expression was significantly down-regulated during HSC activation in vitro.
- Overexpression of miR-29b attenuated the expression of collagen mRNAs (Col1a1, Col1a2) and key HSC activation markers.
- miR-29b overexpression maintained HSCs in a quiescent state and suppressed c-fos mRNA expression, without affecting FAK, ERK, or Akt phosphorylation.
Conclusions:
- miR-29b plays a critical role in suppressing HSC activation.
- Down-regulation of miR-29b is associated with HSC activation and progression of liver fibrosis.
- miR-29b represents a potential therapeutic target for inhibiting HSC activation and treating liver fibrosis.
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