MUC4 is overexpressed in idiopathic pulmonary fibrosis and collaborates with transforming growth factor β inducing fibrotic responses
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Otros documentos de la autoría: MILARA, JAVIER; Ballester, Beatriz; Safont, M. J.; Artigues, Enrique; Escrivá, Juan; Morcillo, Esteban; Cortijo, Julio
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https://doi.org/10.1038/s41385-020-00343-w |
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Título
MUC4 is overexpressed in idiopathic pulmonary fibrosis and collaborates with transforming growth factor β inducing fibrotic responsesAutoría
Fecha de publicación
2020-09-04Editor
Springer Nature; Society of Mucosal ImmunologyISSN
1933-0219; 1935-3456Cita bibliográfica
Milara, J., Ballester, B., Safont, M.J. et al. MUC4 is overexpressed in idiopathic pulmonary fibrosis and collaborates with transforming growth factor β inducing fibrotic responses. Mucosal Immunol 14, 377–388 (2021). https://doi.org/10.1038/s41385-020-00343-wTipo de documento
info:eu-repo/semantics/articleVersión de la editorial
https://www.nature.com/mi/Versión
info:eu-repo/semantics/publishedVersionResumen
Several mucins are implicated in idiopathic pulmonary fibrosis (IPF); however, there is no evidence regarding the role of MUC4 in the development of IPF. Here we demonstrated that MUC4 was overexpressed in IPF patients ... [+]
Several mucins are implicated in idiopathic pulmonary fibrosis (IPF); however, there is no evidence regarding the role of MUC4 in the development of IPF. Here we demonstrated that MUC4 was overexpressed in IPF patients (n = 22) compared with healthy subjects (n = 21) and located in pulmonary arteries, bronchial epithelial cells, fibroblasts, and hyperplastic alveolar type II cells. Decreased expression of MUC4 using siRNA–MUC4 inhibited the mesenchymal/myofibroblast transformations of alveolar type II A549 cells and lung fibroblasts, as well as cell senescence and fibroblast proliferation induced by TGF-β1. The induction of the overexpression of MUC4 increased the effects of TGF-β1 on mesenchymal/myofibroblast transformations and cell senescence. MUC4 overexpression and siRNA–MUC4 gene silencing increased or decreased, respectively, the phosphorylation of TGFβRI and SMAD3, contributing to smad-binding element activation. Immunoprecipitation analysis and confocal immunofluorescence showed the formation of a protein complex between MUC4β/p-TGFβRI and p-SMAD3 in the cell membrane after TGF-β1 stimulation and in lung tissue from IPF patients. Bleomycin-induced lung fibrosis was reduced in mice transiently transfected with siRNA–MUC4. This study shows that MUC4 expression is enhanced in IPF and promotes fibrotic processes in collaboration with TGF-β1 canonical pathway that could be an attractive druggable target for human IPF. [-]
Publicado en
Mucosal Immunology volume 14, pages377–388 (2021)Datos relacionados
https://static-content.springer.com/esm/art%3A10.1038%2Fs41385-020-00343-w/MediaObjects/41385_2020_343_MOESM1_ESM.pdfEntidad financiadora
Fondo Europeo de Desarrollo Regional (FEDER) | Instituto de Salud Carlos III | Generalitat Valenciana | Gobierno de España
Código del proyecto o subvención
FIS PI17/02158 (J.M.) | JR18/00050 (J.M.) | SAF2017-82913-R (J.C.) | RTI2018-096827-B-I00 (E.M.) | CIBERES (CB06/06/0027) | TRA2009-0311 | Prometeo 2017/023/UV (J.C., E.M.) | ACIF/2016/341 (B.B.)
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© Society for Mucosal Immunology 2020
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