TGF-β signaling plays an important role in resisting γ-irradiation

Exp Cell Res. 2013 Feb 15;319(4):466-73. doi: 10.1016/j.yexcr.2012.12.008. Epub 2012 Dec 19.

Abstract

Transforming growth factor-β1 (TGF-β1) regulates various biological processes, including differentiation, bone remodeling and angiogenesis, and is particularly important as a regulator of homeostasis and cell growth in normal tissue. Interestingly, some studies have reported that TGF-β1 induces apoptosis through induction of specific genes, whereas others suggest that TGF-β1 inhibits apoptosis and facilitates cell survival. Resolving these discrepancies, which may reflect differences in cellular context, is an important research priority. Here, using the parental mink lung epithelial cell line, Mv1Lu, and its derivatives, R1B and DR26, lacking TGF-β receptors, we investigated the involvement of TGF-β signaling in the effects of γ-irradiation. We found that canonical TGF-β signaling played an important role in protecting cells from γ-irradiation. Introduction of functional TGF-β receptors or constitutively active Smads into R1B and DR26 cell lines reduced DNA fragmentation, Caspase-3 cleavage and γ-H2AX foci formation in γ-irradiated cells. Notably, we also found that de novo protein synthesis was required for the radio-resistant effects of TGF-β1. Our data thus indicate that TGF-β1 protected against γ-irradiation, decreasing DNA damage and reducing apoptosis, and thereby enhanced cell survival.

Publication types

  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Apoptosis / genetics
  • Apoptosis / radiation effects
  • Cell Survival / drug effects
  • Cell Survival / genetics
  • Cell Survival / radiation effects
  • Cells, Cultured
  • Epithelial Cells / drug effects
  • Epithelial Cells / metabolism
  • Epithelial Cells / physiology
  • Epithelial Cells / radiation effects
  • Gamma Rays*
  • Lung / cytology
  • Lung / drug effects
  • Lung / metabolism
  • Lung / radiation effects
  • Mink
  • Radiation Tolerance* / drug effects
  • Radiation Tolerance* / genetics
  • Radiation Tolerance* / physiology
  • Radiation-Protective Agents / metabolism
  • Radiation-Protective Agents / pharmacology
  • Receptors, Transforming Growth Factor beta / genetics
  • Receptors, Transforming Growth Factor beta / metabolism
  • Receptors, Transforming Growth Factor beta / physiology
  • Signal Transduction / drug effects
  • Signal Transduction / genetics
  • Signal Transduction / physiology
  • Transfection
  • Transforming Growth Factor beta / metabolism
  • Transforming Growth Factor beta / pharmacology
  • Transforming Growth Factor beta / physiology*

Substances

  • Radiation-Protective Agents
  • Receptors, Transforming Growth Factor beta
  • Transforming Growth Factor beta