Nox4 modulates collagen production stimulated by transforming growth factor ß1 in vivo and in vitro.
Biochem Biophys Res Commun
; 430(3): 918-25, 2013 Jan 18.
Article
em En
| MEDLINE
| ID: mdl-23261430
ABSTRACT
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) ß(1) on collagen production in vitro and in vivo. TGFß(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, TGFß(1)-induced hydrogen peroxide production and collagen production were abrogated, suggesting that Nox4-dependent ROS are important for TGFß(1) signaling in collagen production. This was confirmed by the inhibitory effect of an adenovirus carrying siRNA targeting Nox4 (Adv-Nox4i) on TGFß(1)-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 TGFß(1) on collagen accumulation in vivo. TGFß(1)-induced collagen accumulation was significantly reduced when the sponges were instilled with Adv-Nox4(ΔNADPH). In conclusion, Nox4 acts as an intermediary in the signaling of TGFß(1) to facilitate collagen synthesis.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Colágeno
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NADPH Oxidases
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Fator de Crescimento Transformador beta1
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2013
Tipo de documento:
Article