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Potential role of Hedgehog signaling and microRNA-29 in liver fibrosis of IKKβ-deficient mouse.

Publication ,  Journal Article
Hyun, J; Choi, SS; Diehl, AM; Jung, Y
Published in: J Mol Histol
February 2014

Recent studies have reported that NF-κB mediated down-regulation of miRNA-29 and lower expression of miRNA-29 promoted the deposition of collagens in fibrotic liver. Our previous research demonstrated that the increased Hedgehog (Hh) signaling, a key regulator for hepatic fibrogenesis, induced the severe hepatic fibrosis in the livers with impaired NF-κB signaling. These findings led us to investigate the effect of Hh and miRNA-29 on the hepatic fibrosis under dysregulated NF-κB signaling. In this study, we used IKKβ(F/F) and IKKβ-deficient IKKβ(ΔHEP) mouse model with a defective NF-κB signaling pathway, and assessed the expression of the miRNA-29 family (miRNA-29a, miRNA-29b, and miRNA-29c), Hh, and proliferation of MF-HSCs in liver from IKKβ(F/F) mice and IKKβ(ΔHEP) mice both before and after MCDE treatment. The activation of NF-κB was significantly increased in MCDE diet-fed IKKβ(F/F) mice compared to IKKβ(ΔHEP) mice. Expression of miRNA-29 family was greater in MCDE diet-fed IKKβ(ΔHEP) mice than IKKβ(F/F) mice, demonstrating that the impaired NF-κB pathway was unable to suppress the expression of miRNA-29s after injury. However, expression of the Hh signaling pathway was greatly enhanced, and activation of Hh promoted the accumulation of MF-HSCs with impaired NF-κB, eventually increasing fibrogenesis in the damaged liver of IKKβ(ΔHEP) mice. Therefore, these results demonstrated that Hh signaling regulates the proliferation of MF-HSCs irrespective of the action of miRNA-29, eventually contributing hepatic fibrosis, when the NF-κB pathway is disrupted.

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Published In

J Mol Histol

DOI

EISSN

1567-2387

Publication Date

February 2014

Volume

45

Issue

1

Start / End Page

103 / 112

Location

Netherlands

Related Subject Headings

  • Signal Transduction
  • NF-kappa B
  • MicroRNAs
  • Mice, Knockout
  • Mice
  • Liver Cirrhosis
  • I-kappa B Kinase
  • Hepatic Stellate Cells
  • Hedgehog Proteins
  • Gene Expression
 

Citation

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Hyun, J., Choi, S. S., Diehl, A. M., & Jung, Y. (2014). Potential role of Hedgehog signaling and microRNA-29 in liver fibrosis of IKKβ-deficient mouse. J Mol Histol, 45(1), 103–112. https://doi.org/10.1007/s10735-013-9532-5
Hyun, Jeongeun, Steve S. Choi, Anna Mae Diehl, and Youngmi Jung. “Potential role of Hedgehog signaling and microRNA-29 in liver fibrosis of IKKβ-deficient mouse.J Mol Histol 45, no. 1 (February 2014): 103–12. https://doi.org/10.1007/s10735-013-9532-5.
Hyun J, Choi SS, Diehl AM, Jung Y. Potential role of Hedgehog signaling and microRNA-29 in liver fibrosis of IKKβ-deficient mouse. J Mol Histol. 2014 Feb;45(1):103–12.
Hyun, Jeongeun, et al. “Potential role of Hedgehog signaling and microRNA-29 in liver fibrosis of IKKβ-deficient mouse.J Mol Histol, vol. 45, no. 1, Feb. 2014, pp. 103–12. Pubmed, doi:10.1007/s10735-013-9532-5.
Hyun J, Choi SS, Diehl AM, Jung Y. Potential role of Hedgehog signaling and microRNA-29 in liver fibrosis of IKKβ-deficient mouse. J Mol Histol. 2014 Feb;45(1):103–112.
Journal cover image

Published In

J Mol Histol

DOI

EISSN

1567-2387

Publication Date

February 2014

Volume

45

Issue

1

Start / End Page

103 / 112

Location

Netherlands

Related Subject Headings

  • Signal Transduction
  • NF-kappa B
  • MicroRNAs
  • Mice, Knockout
  • Mice
  • Liver Cirrhosis
  • I-kappa B Kinase
  • Hepatic Stellate Cells
  • Hedgehog Proteins
  • Gene Expression