ENAapplication/xmlftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR181/042/SRR18163342/SRR18163342.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR181/041/SRR18163341/SRR18163341.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR181/038/SRR18163338/SRR18163338.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR181/039/SRR18163339/SRR18163339.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR181/043/SRR18163343/SRR18163343.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR181/044/SRR18163344/SRR18163344.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR181/040/SRR18163340/SRR18163340.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR181/033/SRR18163333/SRR18163333.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR181/037/SRR18163337/SRR18163337.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR181/036/SRR18163336/SRR18163336.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR181/034/SRR18163334/SRR18163334.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR181/035/SRR18163335/SRR18163335.fastq.gzprimaryOK200GenomicsDepartment of Pathology and Immunology, University of Geneva Medical Schoolhttps://www.ebi.ac.uk/ena/browser/view/PRJNA810981Mus musculusxref:PubMed:36708644Differentiation of fibroblasts to myofibroblasts is governed by the transforming growth factor beta (TGF-β) through a mechanism involving redox signaling and generation of reactive oxygen species (ROS). Myofibroblasts synthesize proteins of the extracellular matrix and display a contractile phenotype. Myofibroblasts are predominant contributors of wound healing and several pathological states, including fibrotic diseases and cancer. Inhibition of the ROS-generating enzyme NADPH oxidase 4 (NOX4) has been proposed to mitigate fibroblast to myofibroblast differentiation and to offer a therapeutic option for the treatment of fibrotic diseases. In this study, we addressed the role of NOX4 in physiological wound healing and in TGF-β-induced myofibroblast differentiation. We explored the phenotypic changes induced by TGF-β in primary skin fibroblasts isolated from Nox4-deficient mice by immunofluorescence, Western blotting and RNA sequencing. Mice deficient for Cyba, the gene coding for p22phox, a key subunit of NOX4 were used for confirmatory experiments as well as human primary skin fibroblasts. In vivo, the wound healing was similar in wild-type and Nox4-deficient mice. In vitro, despite a strong upregulation following TGF-β treatment, Nox4 did not influence skin myofibroblast differentiation. Nevertheless, up-regulation of the mitochondrial protein Ucp2 and the stress-response protein Hddc3, as well as down-regulation of Islr were observed in Nox4-deficient fibroblasts. Altogether, we provide extensive evidence challenging a profibrotic role of NOX4 in skin fibroblasts and show that Nox4 regulates Ucp2 and Hddc3 expression, suggesting the presence of a so far undescribed redox crosstalk between NOX4 and redox homeostasis in fibroblasts. Overall design: WT and NOX4 KO primary mouse skin fibroblasts were stimulated with 10ng/ml TGF-beta 2 in three biological replicates, total 12 samples were analyzedENAfalseThe role of NOX4 in skin fibroblastsThe role of NOX4 in skin fibroblasts2025-09-242023-03-17PRJNA810981GSE1975621009036708644