Nox4 modulates collagen production stimulated by transforming growth factor beta 1 in vivo and in vitro
Elsa C Chan, Hitesh M Peshavariya, Guei-Sheung Liu, Fan Jiang, Shiang-Yong Lim, Gregory J Dusting
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | ACADEMIC PRESS INC ELSEVIER SCIENCE | Published : 2013
The synthesis of extracellular matrix including collagen during wound healing responses involves signaling via reactive oxygen species (ROS). We hypothesized that NADPH oxidase isoform Nox4 facilitates the stimulatory effects of the profibrotic cytokine transforming growth factor (TGF) β(1) on collagen production in vitro and in vivo. TGFβ(1) stimulated collagen synthesis and hydrogen peroxide generation in mouse cardiac fibroblasts, and both responses were attenuated by a scavenger of superoxide and hydrogen peroxide (EUK-134). Furthermore, by expressing a dominant negative form of Nox4 (Adv-Nox4(ΔNADPH)) in fibroblasts, TGFβ(1)-induced hydrogen peroxide production and collagen production w..View full abstract
Awarded by National Heart Foundation Australia
Awarded by Natural Science Foundation of China
We thanked Professor John F Keaney from the University of Massachusetts Medical School, USA for providing Adv-Nox4i and Dr Barry Goldstein from Thomas Jefferson University, Philadelphia, USA for providing Adv-Nox4<SUP>Delta NADPH</SUP>. HMP is supported by Post-Doc Fellowship (PF 11 M 6093) from National Heart Foundation Australia. F.J. is supported by a grant from Natural Science Foundation of China (Grant Number 81070164). The O'Brien Institute acknowledges the Victorian State Government's Department of Innovation, Industry and Regional Development's Operational Infrastructure Support Program.