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
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/57423
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/57423
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling 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 Técnicas2025-10-22T11:02:04Zoai: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:34982025-10-22 11:02:04.486CONICET 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
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv 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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