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MUC4 is overexpressed in idiopathic pulmonary fibrosis and collaborates with transforming growth factor β inducing fibrotic responses
dc.contributor.author | MILARA, JAVIER | |
dc.contributor.author | Ballester, Beatriz | |
dc.contributor.author | Safont, M. J. | |
dc.contributor.author | Artigues, Enrique | |
dc.contributor.author | Escrivá, Juan | |
dc.contributor.author | Morcillo, Esteban | |
dc.contributor.author | Cortijo, Julio | |
dc.date.accessioned | 2021-10-08T11:51:43Z | |
dc.date.available | 2021-10-08T11:51:43Z | |
dc.date.issued | 2020-09-04 | |
dc.identifier.citation | 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-w | ca_CA |
dc.identifier.issn | 1933-0219 | |
dc.identifier.issn | 1935-3456 | |
dc.identifier.uri | http://hdl.handle.net/10234/194971 | |
dc.description.abstract | 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. | ca_CA |
dc.format.extent | 12 p. | ca_CA |
dc.language.iso | eng | ca_CA |
dc.publisher | Springer Nature | ca_CA |
dc.publisher | Society of Mucosal Immunology | ca_CA |
dc.relation.isPartOf | Mucosal Immunology volume 14, pages377–388 (2021) | ca_CA |
dc.relation.uri | https://static-content.springer.com/esm/art%3A10.1038%2Fs41385-020-00343-w/MediaObjects/41385_2020_343_MOESM1_ESM.pdf | ca_CA |
dc.rights | © Society for Mucosal Immunology 2020 | ca_CA |
dc.rights.uri | http://rightsstatements.org/vocab/InC/1.0/ | ca_CA |
dc.title | MUC4 is overexpressed in idiopathic pulmonary fibrosis and collaborates with transforming growth factor β inducing fibrotic responses | ca_CA |
dc.type | info:eu-repo/semantics/article | ca_CA |
dc.identifier.doi | https://doi.org/10.1038/s41385-020-00343-w | |
dc.rights.accessRights | info:eu-repo/semantics/restrictedAccess | ca_CA |
dc.relation.publisherVersion | https://www.nature.com/mi/ | ca_CA |
dc.type.version | info:eu-repo/semantics/publishedVersion | ca_CA |
project.funder.name | Fondo Europeo de Desarrollo Regional (FEDER) | ca_CA |
project.funder.name | Instituto de Salud Carlos III | ca_CA |
project.funder.name | Generalitat Valenciana | ca_CA |
project.funder.name | Gobierno de España | ca_CA |
oaire.awardNumber | FIS PI17/02158 (J.M.) | ca_CA |
oaire.awardNumber | JR18/00050 (J.M.) | ca_CA |
oaire.awardNumber | SAF2017-82913-R (J.C.) | ca_CA |
oaire.awardNumber | RTI2018-096827-B-I00 (E.M.) | ca_CA |
oaire.awardNumber | CIBERES (CB06/06/0027) | ca_CA |
oaire.awardNumber | TRA2009-0311 | ca_CA |
oaire.awardNumber | Prometeo 2017/023/UV (J.C., E.M.) | ca_CA |
oaire.awardNumber | ACIF/2016/341 (B.B.) | ca_CA |
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