Beta-catenin is a mediator of the response of fibroblasts to irradiation.

Published

Journal Article

Radiation causes soft tissue complications that include fibrosis and deficient wound healing. beta-Catenin, a key component in the canonical Wnt-signaling pathway, is activated in fibrotic processes and wound repair and, as such, could play a role in mediating cellular responses to irradiation. beta-Catenin can form a transcriptionally active complex with members of the Tcf family. A reporter mouse model, in addition to human cell cultures, was used to demonstrate that ionizing radiation activates beta-catenin-mediated, Tcf-dependent transcription both in vitro and in vivo. Furthermore, radiation activates beta-catenin via a Wnt-mediated mechanism, as in the presence of dickkopf-1, an inhibitor of Wnt receptor activation, beta-catenin levels did not increase after irradiation. Fibroblast cell cultures were derived from mice expressing either null or stabilized beta-catenin alleles. Cells expressing stabilized beta-catenin alleles had a higher proliferation rate and formed more colony-forming units than wild-type or null cells after irradiation. Wound healing was studied in these same mice after irradiation. There was a positive correlation between the tensile strength of the wound, the expression levels of type 1 collagen in the skin, and beta-catenin levels. Mice treated with lithium showed increased beta-catenin levels and increased wound strength. beta-Catenin mediates the effects of ionizing radiation in fibroblasts, and its modulation has the potential to decrease the severity of radiation-induced soft tissue complications.

Full Text

Duke Authors

Cited Authors

  • Gurung, A; Uddin, F; Hill, RP; Ferguson, PC; Alman, BA

Published Date

  • January 2009

Published In

Volume / Issue

  • 174 / 1

Start / End Page

  • 248 - 255

PubMed ID

  • 19036807

Pubmed Central ID

  • 19036807

Electronic International Standard Serial Number (EISSN)

  • 1525-2191

Digital Object Identifier (DOI)

  • 10.2353/ajpath.2009.080576

Language

  • eng

Conference Location

  • United States