Hedgehog Signaling is Associated with Liver Response to Fractionated Irradiation in Mice.

Published

Journal Article

BACKGROUND/AIMS:Radiation-induced liver disease (RILD) is a major obstacle in treating liver cancer; however, the mechanisms underlying RILD development remain unclear. Hedgehog (Hh) orchestrates liver response to injury. Herein, we investigated the liver response with Hh to fractionated irradiation (FI) using a small murine model for RILD. METHODS:Male mice exposed to liver-targeted FI with 6Gy in 5 consecutive weekly fractions were sacrificed at one day after weekly irradiation and 6 or 10 weeks post 5th FI for the acute and late response model, respectively. RESULTS:The levels of ALT/AST and apoptosis were elevated in all radiation groups. The expression of Hh ligand, Sonic and Indian Hh, and Hh activator, smoothened and gli2, was higher in the acute groups than the control group. Pro-fibrogenic markers were also up-regulated in this model compared with the control group. Histomorphological changes and ballooned hepatocytes were observed in the late response model. Both the expression of Hh and profibrotic genes and the fibrosis level increased in this model compared with the control groups. CONCLUSION:Enhanced Hedgehog signaling and liver injury with fibrosis in RILD murine model suggests hedgehog as the potential regulator in RILD progression and the suitability of this model for studying RILD.

Full Text

Duke Authors

Cited Authors

  • Kim, J; Wang, S; Hyun, J; Guy, CD; Jung, Y

Published Date

  • January 2016

Published In

Volume / Issue

  • 40 / 1-2

Start / End Page

  • 263 - 276

PubMed ID

  • 27855416

Pubmed Central ID

  • 27855416

Electronic International Standard Serial Number (EISSN)

  • 1421-9778

International Standard Serial Number (ISSN)

  • 1015-8987

Digital Object Identifier (DOI)

  • 10.1159/000452543

Language

  • eng