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Volume 23
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10.3390/ijms23116308
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Article

Oncostatin M Counteracts the Fibrotic Effects of TGF-β1 and IL-4 on Nasal-Polyp-Derived Fibroblasts: A Control of Fibrosis in Chronic Rhinosinusitis with Nasal Polyps?

by
Florent Carsuzaa
1,2,*,
Émilie Béquignon
3,4,
Matthieu Bainaud
1,5,
Jean-François Jégou
1,
Xavier Dufour
1,2,
Jean-Claude Lecron
1,5,† and
Laure Favot
1,†
1
Laboratoire Inflammation Tissus Epithéliaux et Cytokines (LITEC), UR15560, Université de Poitiers, 86000 Poitiers, France
2
Service ORL, Chirurgie Cervico-Maxillo-Faciale et Audiophonologie, Centre Hospitalier Universitaire de Poitiers, 86000 Poitiers, France
3
Service ORL et Chirurgie Cervico-Faciale, Centre Hospitalier Intercommunal de Créteil, 94000 Créteil, France
4
Laboratoire INSERM UMR955 Eq13, Institut Mondor de Recherche Biomédicale, 94000 Créteil, France
5
Service Immunologie et Inflammation, Centre Hospitalier Universitaire de Poitiers, 86021 Poitiers, France
*
Author to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Int. J. Mol. Sci. 2022, 23(11), 6308; https://doi.org/10.3390/ijms23116308
Submission received: 21 April 2022 / Revised: 31 May 2022 / Accepted: 3 June 2022 / Published: 4 June 2022
(This article belongs to the Special Issue OSM/OSMR and Interleukin 6 Family Cytokines in Physiological and Pathological Condition 2.0)
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Abstract

Chronic rhinosinusitis with nasal polyps (CRSwNP) is associated with inflammation and tissue remodeling including myofibroblasts differentiation and extracellular matrix (ECM) deposition mediated by TGF-β1 and IL-4. Oncostatin M (OSM) is a cytokine involved in fibrotic processes in other cellular subtypes. We investigated the mechanisms of action of OSM in the fibrosis process associated with CRSwNP. The expression of IL-4, OSM and TGF-β1 was assessed by RT-qPCR. Primary human cultures of nasal-polyp-derived fibroblasts were established and stimulated by TGF-β1 and/or IL-4 and/or OSM. The expression of ECM components and αSMA was determined by RT-qPCR and Western blot. TGF-β1-Smad3 signaling was investigated by immunofluorescence. TGF-β1, IL-4 and OSM as well as αSMA were overexpressed in nasal polyps when compared to noninflammatory nasal mucosa. In TGF-β1-stimulated nasal-polyp-derived fibroblasts, ECM genes and αSMA gene and protein were overexpressed, as well as αSMA in IL-4-stimulated fibroblasts. OSM counteracted the profibrotic effect of TGF-β1 on ECM components and αSMA. TGF-β1-induced nuclear translocation of Smad3 was completely reversed by OSM. OSM counteracts the profibrotic effect of IL-4 and also TGF-β1, by inhibiting the nuclear translocation of Smad3. We suggest OSM could be an efficient tool to protect against fibrosis in CRSwNP.
Keywords: chronic rhinosinusitis; cytokines; inflammation; nasal polyps; fibroblasts; fibrosis chronic rhinosinusitis; cytokines; inflammation; nasal polyps; fibroblasts; fibrosis

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MDPI and ACS Style

Carsuzaa, F.; Béquignon, É.; Bainaud, M.; Jégou, J.-F.; Dufour, X.; Lecron, J.-C.; Favot, L. Oncostatin M Counteracts the Fibrotic Effects of TGF-β1 and IL-4 on Nasal-Polyp-Derived Fibroblasts: A Control of Fibrosis in Chronic Rhinosinusitis with Nasal Polyps? Int. J. Mol. Sci. 2022, 23, 6308. https://doi.org/10.3390/ijms23116308

AMA Style

Carsuzaa F, Béquignon É, Bainaud M, Jégou J-F, Dufour X, Lecron J-C, Favot L. Oncostatin M Counteracts the Fibrotic Effects of TGF-β1 and IL-4 on Nasal-Polyp-Derived Fibroblasts: A Control of Fibrosis in Chronic Rhinosinusitis with Nasal Polyps? International Journal of Molecular Sciences. 2022; 23(11):6308. https://doi.org/10.3390/ijms23116308

Chicago/Turabian Style

Carsuzaa, Florent, Émilie Béquignon, Matthieu Bainaud, Jean-François Jégou, Xavier Dufour, Jean-Claude Lecron, and Laure Favot. 2022. "Oncostatin M Counteracts the Fibrotic Effects of TGF-β1 and IL-4 on Nasal-Polyp-Derived Fibroblasts: A Control of Fibrosis in Chronic Rhinosinusitis with Nasal Polyps?" International Journal of Molecular Sciences 23, no. 11: 6308. https://doi.org/10.3390/ijms23116308

APA Style

Carsuzaa, F., Béquignon, É., Bainaud, M., Jégou, J.-F., Dufour, X., Lecron, J.-C., & Favot, L. (2022). Oncostatin M Counteracts the Fibrotic Effects of TGF-β1 and IL-4 on Nasal-Polyp-Derived Fibroblasts: A Control of Fibrosis in Chronic Rhinosinusitis with Nasal Polyps? International Journal of Molecular Sciences, 23(11), 6308. https://doi.org/10.3390/ijms23116308

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