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Nox4 modulates collagen production stimulated by transforming growth factor β1 in vivo and in vitro
journal contributionposted on 2023-05-19, 10:47 authored by Chan, EC, Peshavariya, HM, Guei-Sheung LiuGuei-Sheung Liu, Jiang, F, Lim, SY, Dusting, GJ
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) β1 on collagen production in vitro and in vivo. TGFβ1 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-Nox4ΔNADPH) in fibroblasts, TGFβ1-induced hydrogen peroxide production and collagen production were abrogated, suggesting that Nox4-dependent ROS are important for TGFβ1 signaling in collagen production. This was confirmed by the inhibitory effect of an adenovirus carrying siRNA targeting Nox4 (Adv-Nox4i) on TGFβ1-induced collagen synthesis and expression of activated myofibroblasts marker smooth muscle alpha actin. Finally we used a mouse model of subcutaneous sponge implant to examine the role of Nox4 in the local stimulatory effects of TGFβ1 on collagen accumulation in vivo. TGFβ1-induced collagen accumulation was significantly reduced when the sponges were instilled with Adv-Nox4ΔNADPH. In conclusion, Nox4 acts as an intermediary in the signaling of TGFβ1 to facilitate collagen synthesis.
Publication titleBiochemical and Biophysical Research Communications
Department/SchoolMenzies Institute for Medical Research
PublisherAcademic Press Inc Elsevier Science
Place of publication525 B St, Ste 1900, San Diego, USA, Ca, 92101-4495
Rights statementCopyright 2012 Elsevier Inc.