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Nox4 modulates collagen production stimulated by transforming growth factor β1 in vivo and in vitro
Chan, EC and Peshavariya, HM and Liu, GS and Jiang, F and Lim, SY and Dusting, GJ, Nox4 modulates collagen production stimulated by transforming growth factor β1 in vivo and in vitro, Biochemical and Biophysical Research Communications, 430, (3) pp. 918-925. ISSN 0006-291X (2013) [Refereed Article]
Copyright 2012 Elsevier Inc.
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.
|Item Type:||Refereed Article|
|Keywords:||TGFb, Nox4, collagen, fibroblasts, sponge implant|
|Research Division:||Biomedical and Clinical Sciences|
|Research Group:||Medical biotechnology|
|Research Field:||Gene and molecular therapy|
|Objective Group:||Clinical health|
|Objective Field:||Clinical health not elsewhere classified|
|UTAS Author:||Liu, GS (Associate Professor Guei-Sheung Liu)|
|Web of Science® Times Cited:||56|
|Deposited By:||Menzies Institute for Medical Research|
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