TITLE

Fibroblast-to-myofibroblast switch is mediated by NAD(P)H oxidase generated reactive oxygen species

AUTHOR(S)
ALILI, Lirija; SACK, Maren; PUSCHMANN, Katharina; BRENNEISEN, Peter
PUB. DATE
January 2014
SOURCE
Bioscience Reports;2014, Vol. 34 Issue 1, p7
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
Tumour-stroma interaction is a prerequisite for tumour progression in skin cancer. Hereby, a critical step in stromal function is the transition of tumour-associated fibroblasts to MFs (myofibroblasts) by growth factors, for example TGFβ (transforming growth factor beta(). In this study, the question was addressed of whether fibroblast-associated NAD(P)H oxidase (NADH/NADPH oxidase), known to be activated by TGFβ1, is involved in the fibroblast-to-MF switch. The up-regulation of aSMA (alpha smooth muscle actin), a biomarker for MFs, is mediated by a TGFβ1-dependent increase in the intracellular level of ROS (reactive oxygen species). This report demonstrates two novel aspects of the TGFβ1 signalling cascade, namely the generation of ROS due to a biphasic NAD(P)H oxidase activity and a ROSdependent downstream activation of p38 leading to a transition of dermal fibroblasts to MFs that can be inhibited by the selective NAD(P)H oxidase inhibitor apocynin. These data suggest that inhibition of NAD(P)H oxidase activity prevents the fibroblast-to-MF switch and may be important for chemoprevention in context of a 'stromal therapy' which was described earlier
ACCESSION #
95414145

 

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