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Is Nox4 a key regulator of the activated state of fibroblasts in systemic sclerosis?
Author(s) -
Böhm Markus,
Dosoki Heba,
Kerkhoff Claus
Publication year - 2014
Publication title -
experimental dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.108
H-Index - 96
eISSN - 1600-0625
pISSN - 0906-6705
DOI - 10.1111/exd.12497
Subject(s) - nox4 , nadph oxidase , nicotinamide adenine dinucleotide phosphate , regulator , myofibroblast , chemistry , fibrosis , microbiology and biotechnology , gene isoform , endocrinology , medicine , reactive oxygen species , biology , biochemistry , oxidase test , enzyme , gene
The family of nicotinamide adenine dinucleotide phosphate ( NADPH ) oxidases consists of phagocytic gp91 phox and six‐related isoforms. Recent evidence indicates that the NADPH oxidase isoform Nox4 controls vascular, renal and pulmonary injury. We propose that Nox4 is an intrinsic regulator of the activated state of dermal fibroblasts in systemic sclerosis ( SS c). Profibrotic cytokines on the one hand and antifibrogenic factors such as α ‐melanocyte‐stimulating hormone on the other hand may target Nox4 as an intracellular nodal point. Via increased or decreased generation of reactive oxygen species and/or hydrogen peroxide, Nox4 could orchestrate collagen synthesis, differentiation of dermal fibroblasts into a profibrotic myofibroblast phenotype and thus dermal fibrosis. Confirmation of this hypothesis will have important consequences in our understanding of the activated state of dermal fibroblasts in SS c. Based on the availability of clinically useful Nox4 inhibitors, novel antifibrotic therapies of SS c can be envisioned.