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?

被引：13
作者：
Carsuzaa, Florent [1 ,2 ]
Bequignon, Emilie [3 ,4 ]
Bainaud, Matthieu [1 ,5 ]
Jegou, Jean-Francois [1 ]
Dufour, Xavier [1 ,2 ]
Lecron, Jean-Claude [1 ,5 ]
Favot, Laure [1 ]
机构：
[1] Univ Poitiers, Lab Inflammat Tissus Epitheliaux & Cytokines LITE, UR15560, F-86000 Poitiers, France
[2] CHU Poitiers, Serv ORL Chirurg Cervicomaxillofaciale & Audiopho, F-86000 Poitiers, France
[3] Ctr Hosp Intercommunal Creteil, Serv ORL & Chirurg Cervicofaciale, F-94000 Creteil, France
[4] Inst Mondor Rech Biomed, Lab INSERM UMR955 Eq13, F-94000 Creteil, France
[5] CHU Poitiers, Serv Immunol & Inflammat, F-86073 Poitiers, France
来源：
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES | 2022年 / 23卷 / 11期
关键词：
chronic rhinosinusitis; cytokines; inflammation; nasal polyps; fibroblasts; fibrosis; GROWTH-FACTOR-BETA; SKIN INFLAMMATION; CELLS; PROLIFERATION; EXPRESSION; FEATURES;
D O I：
10.3390/ijms23116308
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
Chronic rhinosinusitis with nasal polyps (CRSwNP) is associated with inflammation and tissue remodeling including myofibroblasts differentiation and extracellular matrix (ECM) deposition mediated by TGF-beta 1 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-beta 1 was assessed by RT-qPCR. Primary human cultures of nasal-polyp-derived fibroblasts were established and stimulated by TGF-beta 1 and/or IL-4 and/or OSM. The expression of ECM components and alpha SMA was determined by RT-qPCR and Western blot. TGF-beta 1-Smad3 signaling was investigated by immunofluorescence. TGF-beta 1, IL-4 and OSM as well as alpha SMA were overexpressed in nasal polyps when compared to noninflammatory nasal mucosa. In TGF-beta 1-stimulated nasal-polyp-derived fibroblasts, ECM genes and alpha SMA gene and protein were overexpressed, as well as alpha SMA in IL-4-stimulated fibroblasts. OSM counteracted the profibrotic effect of TGF-beta 1 on ECM components and alpha SMA. TGF-beta 1-induced nuclear translocation of Smad3 was completely reversed by OSM. OSM counteracts the profibrotic effect of IL-4 and also TGF-beta 1, by inhibiting the nuclear translocation of Smad3. We suggest OSM could be an efficient tool to protect against fibrosis in CRSwNP.
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页数：9
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