In vitro analysis of transforming growth factor-beta 1 inhibition in novel Transgenic SBE-luciferase mice ANNALS OF PLASTIC SURGERY Satterwhite, T. S., Chong, A. K., Luo, J., Pham, H., Costa, M., Longaker, M. T., Wyss-Coray, T., Chang, J. 2007; 59 (2): 207-213

Abstract

Transforming growth factor beta1 (TGF-beta1) expression correlates with scarring. A novel transgenic mouse model with a Smad2/3-responsive luciferase reporter construct (SBE-luc) has been developed. We hypothesized that bioluminescence in SBE-luc dermal fibroblasts could be measured to assess TGF-beta1 inhibition.Cultured dermal fibroblasts from SBE-luc mice were treated simultaneously with TGF-beta1 and increasing doses of either neutralizing antibody to TGF-beta (NA-TGFbeta) or SB-431542, a novel TGF-beta receptor kinase inhibitor. Fibroblasts were measured for luciferase activity. SBE-luc fibroblasts underwent Western blot analysis for collagen type I production.TGF-beta1 produced maximal luciferase activity in SBE-luc fibroblasts at 0.1 ng/mL (P < 0.05). NA-TGFbeta and SB-431542 inhibited luciferase activity in a dose-dependent fashion, with complete inhibition achieved by 0.1 microg/mL and 1 microM, respectively (P < 0.05). NA-TGFbeta and SB-431542 inhibited collagen type I production.Our in vitro results provide validation for further in vivo real-time imaging studies using the SBE-luc mouse as a novel wound-healing model.

View details for DOI 10.1097/01.sap.0000252732.25168.34

View details for Web of Science ID 000248363400017

View details for PubMedID 17667417