Dnmt3b knock-down in enteric precursors reveals a possible mechanism by which this de novo methyltransferase is involved in the enteric nervous system development and the onset of Hirschsprung disease

Hirschsprung disease (HSCR, OMIM 142623) is a pathology that shows a lack of enteric ganglia along of the distal gastrointestinal tract. This aganglionosis is attributed to an abnormal proliferation, migration, differentiation and/or survival of enteric precursor cells (EPCs) derived from neural cre...

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Authors: Torroglosa, Ana, Villalba Benito, Leticia, Fernández, Raquel, Moya Jiménez, María José, Antiñolo Gil, Guillermo, Borrego López, Salud
Format: article
Status:Published version
Publication Date:2017
Country:España
Institution:Universidad de Sevilla (US)
Repository:idUS. Depósito de Investigación de la Universidad de Sevilla
OAI Identifier:oai:idus.us.es:11441/96642
Online Access:https://hdl.handle.net/11441/96642
https://doi.org/10.18632/oncotarget 22473
Access Level:Open access
Keyword:Hirschsprung disease
DNMT3b
ENS development
P53
P21
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spelling Dnmt3b knock-down in enteric precursors reveals a possible mechanism by which this de novo methyltransferase is involved in the enteric nervous system development and the onset of Hirschsprung diseaseTorroglosa, AnaVillalba Benito, LeticiaFernández, RaquelMoya Jiménez, María JoséAntiñolo Gil, GuillermoBorrego López, SaludHirschsprung diseaseDNMT3bENS developmentP53P21Hirschsprung disease (HSCR, OMIM 142623) is a pathology that shows a lack of enteric ganglia along of the distal gastrointestinal tract. This aganglionosis is attributed to an abnormal proliferation, migration, differentiation and/or survival of enteric precursor cells (EPCs) derived from neural crest cells (NCCs) during the enteric nervous system (ENS) embryogenesis. DNMT3b de novo methyltransferase is associated with NCCs development and has been shown to be implicated in ENS formation as well as in HSCR. In this study we have aimed to elucidate the specific mechanism underlying the DNMT3b role in such processes. We have performed the knockdown of Dnmt3b expression (Dnmt3b-KD) in enteric precursor cells (EPCs) to clarify its role on these cells in vitro. Moreover, we have analyzed several signaling pathways to determine the mechanisms responsible for the effect caused by Dnmt3b- KD in EPCs. Our results seem to support that Dnmt3b-KD promotes an increase EPCs proliferation that may be mediated by P53 and P21 activity, since both proteins were observed to be down-regulated in our Dnmt3b-KD cultures. Moreover, we observed a down-regulation of P53 and P21 in HSCR patients. These results lead us to propose that DNMT3b could be involved in HSCR through P53 and P21 activity.Instituto de Salud Carlos III PI16/01422Junta de Andalucía CTS-7447Impact JournalsCirugíaCTS-106: Genética médica en Ciencias de la Salud2017info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfapplication/pdfhttps://hdl.handle.net/11441/96642https://doi.org/10.18632/oncotarget 22473reponame:idUS. Depósito de Investigación de la Universidad de Sevillainstname:Universidad de Sevilla (US)InglésOncotarget, 8 (63), 106443-106453.info:eu-repo/semantics/openAccessoai:idus.us.es:11441/966422026-06-17T12:51:07Z
dc.title.none.fl_str_mv Dnmt3b knock-down in enteric precursors reveals a possible mechanism by which this de novo methyltransferase is involved in the enteric nervous system development and the onset of Hirschsprung disease
title Dnmt3b knock-down in enteric precursors reveals a possible mechanism by which this de novo methyltransferase is involved in the enteric nervous system development and the onset of Hirschsprung disease
spellingShingle Dnmt3b knock-down in enteric precursors reveals a possible mechanism by which this de novo methyltransferase is involved in the enteric nervous system development and the onset of Hirschsprung disease
Torroglosa, Ana
Hirschsprung disease
DNMT3b
ENS development
P53
P21
title_short Dnmt3b knock-down in enteric precursors reveals a possible mechanism by which this de novo methyltransferase is involved in the enteric nervous system development and the onset of Hirschsprung disease
title_full Dnmt3b knock-down in enteric precursors reveals a possible mechanism by which this de novo methyltransferase is involved in the enteric nervous system development and the onset of Hirschsprung disease
title_fullStr Dnmt3b knock-down in enteric precursors reveals a possible mechanism by which this de novo methyltransferase is involved in the enteric nervous system development and the onset of Hirschsprung disease
title_full_unstemmed Dnmt3b knock-down in enteric precursors reveals a possible mechanism by which this de novo methyltransferase is involved in the enteric nervous system development and the onset of Hirschsprung disease
title_sort Dnmt3b knock-down in enteric precursors reveals a possible mechanism by which this de novo methyltransferase is involved in the enteric nervous system development and the onset of Hirschsprung disease
dc.creator.none.fl_str_mv Torroglosa, Ana
Villalba Benito, Leticia
Fernández, Raquel
Moya Jiménez, María José
Antiñolo Gil, Guillermo
Borrego López, Salud
author Torroglosa, Ana
author_facet Torroglosa, Ana
Villalba Benito, Leticia
Fernández, Raquel
Moya Jiménez, María José
Antiñolo Gil, Guillermo
Borrego López, Salud
author_role author
author2 Villalba Benito, Leticia
Fernández, Raquel
Moya Jiménez, María José
Antiñolo Gil, Guillermo
Borrego López, Salud
author2_role author
author
author
author
author
dc.contributor.none.fl_str_mv Cirugía
CTS-106: Genética médica en Ciencias de la Salud
dc.subject.none.fl_str_mv Hirschsprung disease
DNMT3b
ENS development
P53
P21
topic Hirschsprung disease
DNMT3b
ENS development
P53
P21
description Hirschsprung disease (HSCR, OMIM 142623) is a pathology that shows a lack of enteric ganglia along of the distal gastrointestinal tract. This aganglionosis is attributed to an abnormal proliferation, migration, differentiation and/or survival of enteric precursor cells (EPCs) derived from neural crest cells (NCCs) during the enteric nervous system (ENS) embryogenesis. DNMT3b de novo methyltransferase is associated with NCCs development and has been shown to be implicated in ENS formation as well as in HSCR. In this study we have aimed to elucidate the specific mechanism underlying the DNMT3b role in such processes. We have performed the knockdown of Dnmt3b expression (Dnmt3b-KD) in enteric precursor cells (EPCs) to clarify its role on these cells in vitro. Moreover, we have analyzed several signaling pathways to determine the mechanisms responsible for the effect caused by Dnmt3b- KD in EPCs. Our results seem to support that Dnmt3b-KD promotes an increase EPCs proliferation that may be mediated by P53 and P21 activity, since both proteins were observed to be down-regulated in our Dnmt3b-KD cultures. Moreover, we observed a down-regulation of P53 and P21 in HSCR patients. These results lead us to propose that DNMT3b could be involved in HSCR through P53 and P21 activity.
publishDate 2017
dc.date.none.fl_str_mv 2017
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/11441/96642
https://doi.org/10.18632/oncotarget 22473
url https://hdl.handle.net/11441/96642
https://doi.org/10.18632/oncotarget 22473
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Oncotarget, 8 (63), 106443-106453.
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Impact Journals
publisher.none.fl_str_mv Impact Journals
dc.source.none.fl_str_mv reponame:idUS. Depósito de Investigación de la Universidad de Sevilla
instname:Universidad de Sevilla (US)
instname_str Universidad de Sevilla (US)
reponame_str idUS. Depósito de Investigación de la Universidad de Sevilla
collection idUS. Depósito de Investigación de la Universidad de Sevilla
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,301603

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