dc.creator | Ruiz Ferrer, Macarena | es |
dc.creator | Torroglosa, Ana | es |
dc.creator | Núñez-Torres, Rocío | es |
dc.creator | Agustín, Juan Carlos de | es |
dc.creator | Antiñolo Gil, Guillermo | es |
dc.creator | Borrego, Salud | es |
dc.date.accessioned | 2021-06-22T17:08:53Z | |
dc.date.available | 2021-06-22T17:08:53Z | |
dc.date.issued | 2011-08-12 | |
dc.identifier.citation | Ruiz Ferrer, M., Torroglosa, A., Núñez-Torres, R., Agustín, J.C.d., Antiñolo Gil, G. y Borrego, S. (2011). Expression of PROKR1 and PROKR2 in Human Enteric Neural Precursor Cells and Identification of Sequence Variants Suggest a Role in HSCR. PLoS ONE, 6 (8), art. n.23475. | |
dc.identifier.issn | 1932-6203 (electrónico) | es |
dc.identifier.uri | https://hdl.handle.net/11441/114721 | |
dc.description.abstract | Background: The enteric nervous system (ENS) is entirely derived from neural crest and its normal development is regulated
by specific molecular pathways. Failure in complete ENS formation results in aganglionic gut conditions such as
Hirschsprung’s disease (HSCR). Recently, PROKR1 expression has been demonstrated in mouse enteric neural crest derived
cells and Prok-1 was shown to work coordinately with GDNF in the development of the ENS.
Principal Findings: In the present report, ENS progenitors were isolated and characterized from the ganglionic gut from
children diagnosed with and without HSCR, and the expression of prokineticin receptors was examined. Immunocytochemical analysis of neurosphere-forming cells demonstrated that both PROKR1 and PROKR2 were present in human
enteric neural crest cells. In addition, we also performed a mutational analysis of PROKR1, PROKR2, PROK1 and PROK2 genes
in a cohort of HSCR patients, evaluating them for the first time as susceptibility genes for the disease. Several missense
variants were detected, most of them affecting highly conserved amino acid residues of the protein and located in
functional domains of both receptors, which suggests a possible deleterious effect in their biological function.
Conclusions: Our results suggest that not only PROKR1, but also PROKR2 might mediate a complementary signalling to the RET/
GFRa1/GDNF pathway supporting proliferation/survival and differentiation of precursor cells during ENS development. These
findings, together with the detection of sequence variants in PROKR1, PROK1 and PROKR2 genes associated to HSCR and, in some
cases in combination with RET or GDNF mutations, provide the first evidence to consider them as susceptibility genes for HSCR. | es |
dc.description.sponsorship | Fondo de Investigación Sanitaria, Spain (PI070080, PI1001290 and PI071315 for the E-Rare project) | es |
dc.description.sponsorship | Consejería de Innovación Ciencia y Empresa de la Junta de Andalucía (CTS 2590) | es |
dc.description.sponsorship | Consejería de Salud de la Junta de Andalucía (PI0249-2008) | es |
dc.format | application/pdf | es |
dc.format.extent | 7 p. | es |
dc.language.iso | eng | es |
dc.publisher | Public Library of Science | es |
dc.relation.ispartof | PLoS ONE, 6 (8), art. n.23475. | |
dc.rights | Attribution-NonCommercial-NoDerivatives 4.0 Internacional | * |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/ | * |
dc.subject | PROKR1 | es |
dc.subject | PROKR2 | es |
dc.subject | Enteric nervous system | es |
dc.subject | Hirschsprung’s disease | es |
dc.title | Expression of PROKR1 and PROKR2 in Human Enteric Neural Precursor Cells and Identification of Sequence Variants Suggest a Role in HSCR | es |
dc.type | info:eu-repo/semantics/article | es |
dcterms.identifier | https://ror.org/03yxnpp24 | |
dc.type.version | info:eu-repo/semantics/publishedVersion | es |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | es |
dc.contributor.affiliation | Universidad de Sevilla. Departamento de Cirugía | es |
dc.relation.projectID | PI070080 | es |
dc.relation.projectID | PI1001290 | es |
dc.relation.projectID | PI071315 | es |
dc.relation.projectID | CTS 2590 | es |
dc.relation.projectID | PI0249-2008 | es |
dc.relation.publisherversion | https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0023475 | es |
dc.identifier.doi | 10.1371/journal.pone.0023475 | es |
dc.journaltitle | PLoS ONE | es |
dc.publication.volumen | 6 | es |
dc.publication.issue | 8 | es |
dc.publication.initialPage | art. n.23475 | es |