MCL-1 is modulated in Crohn’s disease fibrosis by miR-29b via IL-6 and IL-8
- Autores
- Nijhuis, Anke; Curciarello, Renata; Mehta, Shameer; Feakins, Roger; Bishop, Cleo L.; Lindsay, James O.; Silver, Andrew
- Año de publicación
- 2017
- Idioma
- inglés
- Tipo de recurso
- artículo
- Estado
- versión publicada
- Descripción
- 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.
Fil: Nijhuis, Anke. Queen Mary University of London; Reino Unido
Fil: Curciarello, Renata. Queen Mary University of London; Reino Unido. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Mehta, Shameer. Queen Mary University of London; Reino Unido
Fil: Feakins, Roger. The Royal London Hospital; Reino Unido
Fil: Bishop, Cleo L.. Queen Mary University of London; Reino Unido
Fil: Lindsay, James O.. Queen Mary University of London; Reino Unido
Fil: Silver, Andrew. Queen Mary University of London; Reino Unido - Materia
-
CROHN’S DISEASE
FIBROSIS
MCL-1
MICRORNA
MIR-29B - Nivel de accesibilidad
- acceso abierto
- Condiciones de uso
- https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
- Repositorio
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/57423
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MCL-1 is modulated in Crohn’s disease fibrosis by miR-29b via IL-6 and IL-8Nijhuis, AnkeCurciarello, RenataMehta, ShameerFeakins, RogerBishop, Cleo L.Lindsay, James O.Silver, AndrewCROHN’S DISEASEFIBROSISMCL-1MICRORNAMIR-29Bhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3The 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.Fil: Nijhuis, Anke. Queen Mary University of London; Reino UnidoFil: Curciarello, Renata. Queen Mary University of London; Reino Unido. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Mehta, Shameer. Queen Mary University of London; Reino UnidoFil: Feakins, Roger. The Royal London Hospital; Reino UnidoFil: Bishop, Cleo L.. Queen Mary University of London; Reino UnidoFil: Lindsay, James O.. Queen Mary University of London; Reino UnidoFil: Silver, Andrew. Queen Mary University of London; Reino UnidoSpringer2017-05info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/57423Nijhuis, 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; 325-3350302-766X1432-0878CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1007/s00441-017-2576-1info:eu-repo/semantics/altIdentifier/url/https://link.springer.com/article/10.1007%2Fs00441-017-2576-1info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:34:02Zoai:ri.conicet.gov.ar:11336/57423instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-29 09:34:02.425CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse |
dc.title.none.fl_str_mv |
MCL-1 is modulated in Crohn’s disease fibrosis by miR-29b via IL-6 and IL-8 |
title |
MCL-1 is modulated in Crohn’s disease fibrosis by miR-29b via IL-6 and IL-8 |
spellingShingle |
MCL-1 is modulated in Crohn’s disease fibrosis by miR-29b via IL-6 and IL-8 Nijhuis, Anke CROHN’S DISEASE FIBROSIS MCL-1 MICRORNA MIR-29B |
title_short |
MCL-1 is modulated in Crohn’s disease fibrosis by miR-29b via IL-6 and IL-8 |
title_full |
MCL-1 is modulated in Crohn’s disease fibrosis by miR-29b via IL-6 and IL-8 |
title_fullStr |
MCL-1 is modulated in Crohn’s disease fibrosis by miR-29b via IL-6 and IL-8 |
title_full_unstemmed |
MCL-1 is modulated in Crohn’s disease fibrosis by miR-29b via IL-6 and IL-8 |
title_sort |
MCL-1 is modulated in Crohn’s disease fibrosis by miR-29b via IL-6 and IL-8 |
dc.creator.none.fl_str_mv |
Nijhuis, Anke Curciarello, Renata Mehta, Shameer Feakins, Roger Bishop, Cleo L. Lindsay, James O. Silver, Andrew |
author |
Nijhuis, Anke |
author_facet |
Nijhuis, Anke Curciarello, Renata Mehta, Shameer Feakins, Roger Bishop, Cleo L. Lindsay, James O. Silver, Andrew |
author_role |
author |
author2 |
Curciarello, Renata Mehta, Shameer Feakins, Roger Bishop, Cleo L. Lindsay, James O. Silver, Andrew |
author2_role |
author author author author author author |
dc.subject.none.fl_str_mv |
CROHN’S DISEASE FIBROSIS MCL-1 MICRORNA MIR-29B |
topic |
CROHN’S DISEASE FIBROSIS MCL-1 MICRORNA MIR-29B |
purl_subject.fl_str_mv |
https://purl.org/becyt/ford/3.1 https://purl.org/becyt/ford/3 |
dc.description.none.fl_txt_mv |
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. Fil: Nijhuis, Anke. Queen Mary University of London; Reino Unido Fil: Curciarello, Renata. Queen Mary University of London; Reino Unido. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Mehta, Shameer. Queen Mary University of London; Reino Unido Fil: Feakins, Roger. The Royal London Hospital; Reino Unido Fil: Bishop, Cleo L.. Queen Mary University of London; Reino Unido Fil: Lindsay, James O.. Queen Mary University of London; Reino Unido Fil: Silver, Andrew. Queen Mary University of London; Reino Unido |
description |
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. |
publishDate |
2017 |
dc.date.none.fl_str_mv |
2017-05 |
dc.type.none.fl_str_mv |
info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion http://purl.org/coar/resource_type/c_6501 info:ar-repo/semantics/articulo |
format |
article |
status_str |
publishedVersion |
dc.identifier.none.fl_str_mv |
http://hdl.handle.net/11336/57423 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 0302-766X 1432-0878 CONICET Digital CONICET |
url |
http://hdl.handle.net/11336/57423 |
identifier_str_mv |
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 0302-766X 1432-0878 CONICET Digital CONICET |
dc.language.none.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
info:eu-repo/semantics/altIdentifier/doi/10.1007/s00441-017-2576-1 info:eu-repo/semantics/altIdentifier/url/https://link.springer.com/article/10.1007%2Fs00441-017-2576-1 |
dc.rights.none.fl_str_mv |
info:eu-repo/semantics/openAccess https://creativecommons.org/licenses/by-nc-sa/2.5/ar/ |
eu_rights_str_mv |
openAccess |
rights_invalid_str_mv |
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/ |
dc.format.none.fl_str_mv |
application/pdf application/pdf application/pdf |
dc.publisher.none.fl_str_mv |
Springer |
publisher.none.fl_str_mv |
Springer |
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Consejo Nacional de Investigaciones Científicas y Técnicas |
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CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas |
repository.mail.fl_str_mv |
dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar |
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13.070432 |