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dc.contributor.author
Nijhuis, Anke
dc.contributor.author
Curciarello, Renata
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dc.contributor.author
Mehta, Shameer
dc.contributor.author
Feakins, Roger
dc.contributor.author
Bishop, Cleo L.
dc.contributor.author
Lindsay, James O.
dc.contributor.author
Silver, Andrew
dc.date.available
2018-08-28T19:53:23Z
dc.date.issued
2017-05
dc.identifier.citation
Nijhuis, Anke; Curciarello, Renata; Mehta, Shameer; Feakins, Roger; Bishop, Cleo L.; et al.; MCL-1 is modulated in Crohn’s disease fibrosis by miR-29b via IL-6 and IL-8; Springer; Cell and Tissue Research; 368; 2; 5-2017; 325-335
dc.identifier.issn
0302-766X
dc.identifier.uri
http://hdl.handle.net/11336/57423
dc.description.abstract
The miR-29 family is involved in fibrosis in multiple organs, including the intestine where miR-29b facilitates TGF-β-mediated up-regulation of collagen in mucosal fibroblasts from Crohn’s disease (CD) patients. Myeloid cell leukemia-1 (MCL-1), a member of the B-cell CLL/Lymphoma 2 (BCL-2) apoptosis family, is involved in liver fibrosis and is targeted by miR-29b via its 3’-UTR in cultured cell lines. We investigate the role of MCL-1 and miR-29b in primary intestinal fibroblasts and tissue from stricturing CD patients. Transfection of CD intestinal fibroblasts with pre-miR-29b resulted in a significant increase in the mRNA expression of MCL-1 isoforms [MCL-1Long (L)/Extra Short (ES) and MCL-1Short (S)], although MCL-1S was expressed at significantly lower levels. Western blotting predominantly detected the anti-apoptotic MCL-1L isoform, and immunofluorescence showed that staining was localised in discrete nuclear foci. Transfection with pre-miR-29b or anti-miR-29b resulted in a significant increase or decrease, respectively, in MCL-1L foci. CD fibroblasts treated with IL-6 and IL-8, inflammatory cytokines upstream of MCL-1, increased the total mass of MCL-1L-positive foci. Furthermore, transfection of intestinal fibroblasts with pre-miR-29b resulted in an increase in mRNA and protein levels of IL-6 and IL-8. Finally, immunohistochemistry showed reduced MCL-1 protein expression in fibrotic CD samples compared to non-stricturing controls. Together, our findings suggest that induction of MCL-1 by IL-6/IL-8 may surmount any direct down-regulation by miR-29b via its 3’-UTR. We propose that an anti-fibrotic miR-29b/IL-6 IL-8/MCL-1L axis may influence intestinal fibrosis in CD. In the future, therapeutic modulation of this pathway might contribute to the management of fibrosis in CD.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
Springer
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dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
Crohn&Rsquo;S Disease
dc.subject
Fibrosis
dc.subject
Mcl-1
dc.subject
Microrna
dc.subject
Mir-29b
dc.subject.classification
Inmunología
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dc.subject.classification
Medicina Básica
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dc.subject.classification
CIENCIAS MÉDICAS Y DE LA SALUD
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dc.title
MCL-1 is modulated in Crohn’s disease fibrosis by miR-29b via IL-6 and IL-8
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2018-08-28T18:42:24Z
dc.identifier.eissn
1432-0878
dc.journal.volume
368
dc.journal.number
2
dc.journal.pagination
325-335
dc.journal.pais
Alemania
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dc.journal.ciudad
Berlin
dc.description.fil
Fil: Nijhuis, Anke. Queen Mary University of London; Reino Unido
dc.description.fil
Fil: Curciarello, Renata. Queen Mary University of London; Reino Unido. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
dc.description.fil
Fil: Mehta, Shameer. Queen Mary University of London; Reino Unido
dc.description.fil
Fil: Feakins, Roger. The Royal London Hospital; Reino Unido
dc.description.fil
Fil: Bishop, Cleo L.. Queen Mary University of London; Reino Unido
dc.description.fil
Fil: Lindsay, James O.. Queen Mary University of London; Reino Unido
dc.description.fil
Fil: Silver, Andrew. Queen Mary University of London; Reino Unido
dc.journal.title
Cell and Tissue Research
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dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1007/s00441-017-2576-1
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/https://link.springer.com/article/10.1007%2Fs00441-017-2576-1
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