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dc.rights.licenseAtribución-SinDerivadas 4.0 Internacional
dc.contributor.advisorUmaña Pérez, Yadi Adriana
dc.contributor.authorCastro Badilla, Juan José
dc.date.accessioned2021-10-25T15:27:11Z
dc.date.available2021-10-25T15:27:11Z
dc.date.issued2021-04-23
dc.identifier.urihttps://repositorio.unal.edu.co/handle/unal/80608
dc.descriptionilustraciones, fotografías, gráficas
dc.description.abstractEl factor de crecimiento similar a la insulina tipo 2, IGF2, ejerce acciones a través de los receptores de la familia IGF incluyendo el receptor tipo 1 (IGF1R), el receptor de insulina (IR) y los híbridos IGF1R/IR. Preferentemente, su acción es mediada a través del receptor IGF1R modulando rutas de señalización intracelulares esenciales en procesos como la proliferación, migración o invasión celular, eventos que son de carácter crucial en las manifestaciones patológicas originadas en el trofoblasto, tales como la enfermedad trofoblástica gestacional, molas, preeclampsia o la restricción de crecimiento intrauterino, siendo estas complicaciones un problema actual para la salud pública del país. Se ha descrito que en tejido de mola la expresión de IGF2 se encuentra elevada y, además, que participa activamente en el proceso de la embriogénesis. La regulación de la biodisponibilidad de este ligando se atribuye, entre otros, a la unión con el receptor IGF2R, el cual lo internaliza para su degradación. Sin embargo, hace más de una década existe controversia sobre si esta interacción lGF2/IGF2R puede desencadenar una vía de señalización que participe en los procesos celulares descritos anteriormente. En este orden de ideas, para explorar si existe una vía de señalización dependiente de IGF2R, sin la activación directa de los otros receptores de la familia, se usó como estrategia estimular células derivadas de trofoblasto humano HTR-8/SVneo con Leu27IGF2, péptido análogo de IGF2, que se une exclusivamente al IGF2R. La inducción de las células con el análogo generó una activación temprana de las proteínas ERK1 y 2 mayor a la inducida por el IGF2. Se observó un incremento en los niveles de transcripción de MMP-9 de carácter tiempo-dependiente de Leu27IGF2 y anticipado con respecto al péptido IGF2, concordante con un aumento temprano de la actividad gelatinasa de MMP-9. Se determinó que la interacción de IGF2R con Leu27IGF2 generó un incremento significativo del 20%, 13% y 23% en adhesión, migración y proliferación celular respectivamente. Resultados que nos sugieren que el IGF2 en células de trofoblasto, activa al receptor IGF2R y al menos una ruta de señalización, como la de MAPKs, involucrada en el aumento de la activación de proteínas y transcripción de genes que favorecen la adhesión, migración e invasión celular durante la implantación blastocística. (Texto tomado de la fuente).
dc.description.abstractThe insulin-like growth fact or type 2, IGF2, exerts actions through receptors in the IGF family including the type 1 receptor (IGF1R), the insulin receptor (IR) and IGF1R/IR hybrids. Preferably, its action is mediated through the IGF1R receptor modulating intracellular signaling pathways essential in processes such as cell proliferation, migration or invasion, events that are crucial in the pathological manifestations originated by the trophoblast, such as gestational trophoblastic diseases, moles, preeclampsia or intrauterine growth restriction, being these complications a current problem for the public health of the country. It has been described that the expression of IGF2 in mole tissue is high and, in addition, that it actively participates in the embryogenesis process. The regulation of the bioavailability of this ligand is attributed, among others, to the binding with the IGF2R receptor which internalizes it for degradation. However, for more than a decade there has been controversy about whether this interaction lGF2/IGF2R can trigger a signaling pathway involved in the cellular processes described above. In this order of ideas to explore if there is an IGF2R-dependent signaling pathway, without the direct activation of the other receptors of the family, a strategy was used to stimulate cells derived from human trophoblast HTR-8/SVneo with Leu27IGF2, an analogous peptide of IGF2, which binds exclusively to IGF2R. The induction of cells with the analogue generated a higher early activation of ERK1 and 2 proteins compared to that induced by IGF2. Similarly, an increase in the transcription levels of Leu27IGF2-dependent and anticipated MMP-9 with respect to IGF2 peptide was observed, consistent with an early increase in MMP-9 gelatinase activity. It was determined that interaction of IGF2R with Leu27IGF2 generated a significant increase of approximately 20%, 13% and 23% in adhesion, migration and cell proliferation respectively with respect to basal condition. These results suggest that IGF2 in trophoblast cells activates the IGF2R receptor and at least one signaling pathway, such as MAPKs, involved in increased protein activation and gene transcription that favor cell adhesion, migration and invasion during blastocyst implantation.
dc.format.extentxvii, 74 páginas
dc.format.mimetypeapplication/pdf
dc.language.isospa
dc.publisherUniversidad Nacional de Colombia
dc.rights.urihttp://creativecommons.org/licenses/by-nd/4.0/
dc.subject.ddc570 - Biología
dc.titleCaracterización de la vía de señalización intracelular mediada por IGF2R en trofoblasto humano
dc.typeTrabajo de grado - Doctorado
dc.type.driverinfo:eu-repo/semantics/doctoralThesis
dc.type.versioninfo:eu-repo/semantics/acceptedVersion
dc.publisher.programBogotá - Ciencias - Doctorado en Ciencias - Bioquímica
dc.contributor.researchgroupGrupo de Investigación en Hormonas
dc.description.degreelevelDoctorado
dc.description.degreenameDoctor en Ciencias - Bioquímica
dc.description.researchareaFactores de crecimiento, diferenciación y cáncer
dc.identifier.instnameUniversidad Nacional de Colombia
dc.identifier.reponameRepositorio Institucional Universidad Nacional de Colombia
dc.identifier.repourlhttps://repositorio.unal.edu.co/
dc.publisher.departmentDepartamento de Química
dc.publisher.facultyFacultad de Ciencias
dc.publisher.placeBogotá, Colombia
dc.publisher.branchUniversidad Nacional de Colombia - Sede Bogotá
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dc.rights.accessrightsinfo:eu-repo/semantics/openAccess
dc.subject.decsReceptor IGF Tipo 2
dc.subject.decsReceptor, IGF Type 2
dc.subject.decsReceptor, IGF Type 1
dc.subject.decsReceptor IGF Tipo 1
dc.subject.decsProteínas Tirosina Quinasas Receptoras
dc.subject.decsReceptor Protein-Tyrosine Kinases
dc.subject.proposalIGF receptor
dc.subject.proposalHTR-8/SVneo
dc.subject.proposalFactor de crecimiento similar a insulina tipo 2
dc.subject.proposalImplantación
dc.subject.proposalPlacenta
dc.subject.proposalObesidad
dc.subject.proposalIGF receptor
dc.subject.proposalInsulin-like growth factor type 2
dc.subject.proposalImplantation
dc.subject.proposalObesity
dc.title.translatedCharacterization of the intracellular signaling mediated by IGF2R in human trophoblast
dc.type.coarhttp://purl.org/coar/resource_type/c_db06
dc.type.coarversionhttp://purl.org/coar/version/c_ab4af688f83e57aa
dc.type.contentText
dc.type.redcolhttp://purl.org/redcol/resource_type/TD
oaire.accessrightshttp://purl.org/coar/access_right/c_abf2
oaire.awardtitle“Caracterización de la vía de señalización intracelular mediada por IGF-IIR en trofoblasto humano”, código Hermes 39172
dcterms.audience.professionaldevelopmentInvestigadores
dcterms.audience.professionaldevelopmentPúblico general
dc.description.curricularareaDepartamento de Química


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