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Hedgehog signaling is critical for normal liver regeneration after partial hepatectomy in mice.

Publication ,  Journal Article
Ochoa, B; Syn, W-K; Delgado, I; Karaca, GF; Jung, Y; Wang, J; Zubiaga, AM; Fresnedo, O; Omenetti, A; Zdanowicz, M; Choi, SS; Diehl, AM
Published in: Hepatology
May 2010

UNLABELLED: Distinct mechanisms are believed to regulate growth of the liver during fetal development and after injury in adults, because the former relies on progenitors and the latter generally involves replication of mature hepatocytes. However, chronic liver injury in adults increases production of Hedgehog (Hh) ligands, developmental morphogens that control progenitor cell fate and orchestrate various aspects of tissue construction during embryogenesis. This raises the possibility that similar Hh-dependent mechanisms also might regulate adult liver regeneration. The current analysis of murine liver regeneration after 70% partial hepatectomy (PH), an established model of adult liver regeneration, demonstrated that PH induced production of Hh ligands and activated Hh signaling in liver cells. Treatment with a specific Hh signaling inhibitor interfered with several key components of normal liver regeneration, significantly inhibiting progenitor responses, matrix remodeling, proliferation of hepatocytes and ductular cells, and restoration of liver mass. These global inhibitory effects on liver regeneration dramatically reduced survival after PH. CONCLUSION: Mechanisms that mediate liver organogenesis, such as Hh pathway activation, are retained and promote reconstruction of adult livers after injury.

Duke Scholars

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Published In

Hepatology

DOI

EISSN

1527-3350

Publication Date

May 2010

Volume

51

Issue

5

Start / End Page

1712 / 1723

Location

United States

Related Subject Headings

  • Veratrum Alkaloids
  • Signal Transduction
  • Mice
  • Male
  • Liver Regeneration
  • Liver Diseases
  • Hepatectomy
  • Hedgehog Proteins
  • Gastroenterology & Hepatology
  • Female
 

Citation

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Ochoa, B., Syn, W.-K., Delgado, I., Karaca, G. F., Jung, Y., Wang, J., … Diehl, A. M. (2010). Hedgehog signaling is critical for normal liver regeneration after partial hepatectomy in mice. Hepatology, 51(5), 1712–1723. https://doi.org/10.1002/hep.23525
Ochoa, Begoña, Wing-Kin Syn, Igotz Delgado, Gamze F. Karaca, Youngmi Jung, Jiangbo Wang, Ana M. Zubiaga, et al. “Hedgehog signaling is critical for normal liver regeneration after partial hepatectomy in mice.Hepatology 51, no. 5 (May 2010): 1712–23. https://doi.org/10.1002/hep.23525.
Ochoa B, Syn W-K, Delgado I, Karaca GF, Jung Y, Wang J, et al. Hedgehog signaling is critical for normal liver regeneration after partial hepatectomy in mice. Hepatology. 2010 May;51(5):1712–23.
Ochoa, Begoña, et al. “Hedgehog signaling is critical for normal liver regeneration after partial hepatectomy in mice.Hepatology, vol. 51, no. 5, May 2010, pp. 1712–23. Pubmed, doi:10.1002/hep.23525.
Ochoa B, Syn W-K, Delgado I, Karaca GF, Jung Y, Wang J, Zubiaga AM, Fresnedo O, Omenetti A, Zdanowicz M, Choi SS, Diehl AM. Hedgehog signaling is critical for normal liver regeneration after partial hepatectomy in mice. Hepatology. 2010 May;51(5):1712–1723.
Journal cover image

Published In

Hepatology

DOI

EISSN

1527-3350

Publication Date

May 2010

Volume

51

Issue

5

Start / End Page

1712 / 1723

Location

United States

Related Subject Headings

  • Veratrum Alkaloids
  • Signal Transduction
  • Mice
  • Male
  • Liver Regeneration
  • Liver Diseases
  • Hepatectomy
  • Hedgehog Proteins
  • Gastroenterology & Hepatology
  • Female