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dc.provenanceCONICET-
dc.creatorNijhuis, Anke-
dc.creatorCurciarello, Renata-
dc.creatorMehta, Shameer-
dc.creatorFeakins, Roger-
dc.creatorBishop, Cleo L.-
dc.creatorLindsay, James O.-
dc.creatorSilver, Andrew-
dc.date2018-08-28T19:53:23Z-
dc.date2018-08-28T19:53:23Z-
dc.date2017-05-
dc.date2018-08-28T18:42:24Z-
dc.date.accessioned2019-04-29T15:33:46Z-
dc.date.available2019-04-29T15:33:46Z-
dc.date.issued2017-05-
dc.identifierNijhuis, 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.identifier0302-766X-
dc.identifierhttp://hdl.handle.net/11336/57423-
dc.identifier1432-0878-
dc.identifierCONICET Digital-
dc.identifierCONICET-
dc.identifier.urihttp://rodna.bn.gov.ar:8080/jspui/handle/bnmm/296592-
dc.descriptionThe 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.descriptionFil: Nijhuis, Anke. Queen Mary University of London; Reino Unido-
dc.descriptionFil: Curciarello, Renata. Queen Mary University of London; Reino Unido. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina-
dc.descriptionFil: Mehta, Shameer. Queen Mary University of London; Reino Unido-
dc.descriptionFil: Feakins, Roger. The Royal London Hospital; Reino Unido-
dc.descriptionFil: Bishop, Cleo L.. Queen Mary University of London; Reino Unido-
dc.descriptionFil: Lindsay, James O.. Queen Mary University of London; Reino Unido-
dc.descriptionFil: Silver, Andrew. Queen Mary University of London; Reino Unido-
dc.formatapplication/pdf-
dc.formatapplication/pdf-
dc.formatapplication/pdf-
dc.languageeng-
dc.publisherSpringer-
dc.relationinfo:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1007/s00441-017-2576-1-
dc.relationinfo:eu-repo/semantics/altIdentifier/url/https://link.springer.com/article/10.1007%2Fs00441-017-2576-1-
dc.rightsinfo:eu-repo/semantics/openAccess-
dc.rightshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/-
dc.sourcereponame:CONICET Digital (CONICET)-
dc.sourceinstname:Consejo Nacional de Investigaciones Científicas y Técnicas-
dc.sourceinstacron:CONICET-
dc.source.urihttp://hdl.handle.net/11336/57423-
dc.subjectCROHN’S DISEASE-
dc.subjectFIBROSIS-
dc.subjectMCL-1-
dc.subjectMICRORNA-
dc.subjectMIR-29B-
dc.subjectInmunología-
dc.subjectMedicina Básica-
dc.subjectCIENCIAS MÉDICAS Y DE LA SALUD-
dc.titleMCL-1 is modulated in Crohn’s disease fibrosis by miR-29b via IL-6 and IL-8-
dc.typeinfo:eu-repo/semantics/article-
dc.typeinfo:eu-repo/semantics/publishedVersion-
dc.typeinfo:ar-repo/semantics/articulo-
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