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Nox4 modulates collagen production stimulated by transforming growth factor β1 in vivo and in vitro.

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) 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 were abrogated, suggesting that Nox4-dependent ROS are important for TGFβ(1) signaling in collagen production. This was confirmed by the inhibitory effect of an adenovirus carrying siRNA targeting Nox4 (Adv-Nox4i) on TGFβ(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 TGFβ(1) on collagen accumulation in vivo. TGFβ(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 TGFβ(1) to facilitate collagen synthesis.

journal_name

Biochem Biophys Res Commun

journal_title

Biochemical and biophysical research communications

authors

Chan EC,Peshavariya HM,Liu GS,Jiang F,Lim SY,Dusting GJ

doi

10.1016/j.bbrc.2012.11.138

subject

Has Abstract

pub_date

2013-01-18 00:00:00

pages

918-25

issue

3

eissn

0006-291X

issn

1090-2104

pii

S0006-291X(12)02400-X

journal_volume

430

pub_type

杂志文章

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