{"id":95762,"date":"2009-04-09T00:00:00","date_gmt":"2009-04-09T00:00:00","guid":{"rendered":"https:\/\/www.deberes.net\/tesis\/sin-categoria\/papel-de-las-isoformas-her-y-la-mtor-en-la-acantolisis-del-penfigo-vulgar-en-un-modelo-murino\/"},"modified":"2009-04-09T00:00:00","modified_gmt":"2009-04-09T00:00:00","slug":"papel-de-las-isoformas-her-y-la-mtor-en-la-acantolisis-del-penfigo-vulgar-en-un-modelo-murino","status":"publish","type":"post","link":"https:\/\/www.deberes.net\/tesis\/dermatologia\/papel-de-las-isoformas-her-y-la-mtor-en-la-acantolisis-del-penfigo-vulgar-en-un-modelo-murino\/","title":{"rendered":"Papel de las isoformas her y la mtor en la acant\u00f3lisis del p\u00e9nfigo vulgar en un modelo murino"},"content":{"rendered":"<h2>Tesis doctoral de <strong> Maider Pretel Irazabal <\/strong><\/h2>\n<p>El p\u00e9nfigo vulgar (pv) es una enfermedad ampollosa autoinmune que afecta a piel y mucosas, caracterizada por la  presencia de autoanticuerpos igg frente a la desmogle\u00edna 3 (dsg3) que provocan una ruptura intraepitelial de la epidermis llamada acant\u00f3lisis. El mecanismo por el cual se produce la acant\u00f3lisis no es del todo conocido. Nuestro objetivo en este trabajo fue investigar los eventos moleculares implicados en el desarrollo y la localizaci\u00f3n de la apoptosis y la acant\u00f3lisis en el pv. Para ello empleamos el modelo murino de transferencia pasiva con estudios de inmunohistoqu\u00edmica con un an\u00e1lisis cuantitativo y la t\u00e9cnica tunel para el estudio de la apoptosis. Tanto las mol\u00e9culas de se\u00f1alizaci\u00f3n activadas analizadas como las c\u00e9lulas apopt\u00f3ticas detectadas mostraron la misma localizaci\u00f3n. Hemos observado por primera vez in vivo un aumento de la expresi\u00f3n de las isoformas activadas de los receptores her en la capa basal de la epidermis en las lesiones de pv. La importancia de este hallazgo se ve reforzada por el hecho de que el pretratamiento de los ratones con erlotinib (inhibidor de her1, her2 y her3) inhibi\u00f3 tanto la enfermedad cl\u00ednica como histol\u00f3gica. Adem\u00e1s, hemos hallado una casi nula expresi\u00f3n de la akt activada comparada con un nivel m\u00e1s elevado de la mtor activada dentro de las c\u00e9lulas basales de la epidermis. Tras el pretratamiento de los animales con rapamicina (inhibidor de mtor) pudimos observar c\u00f3mo se anularon las manifestaciones cl\u00ednicas e histol\u00f3gicas del pv. Nuestras observaciones sugieren que la acant\u00f3lisis podr\u00eda estar restringida a la capa basal, al menos en parte, por el aumento selectivo de las isoformas activadas de los receptores her que ocurre en estas c\u00e9lulas. Despu\u00e9s de la fosforilaci\u00f3n de las isoformas de los receptores her, se activar\u00edan v\u00edas de se\u00f1alizaci\u00f3n intracelular en la capa basal epid\u00e9rmica. Adem\u00e1s, el desequilibrio de akt\/mtor que tiene lugar en las c\u00e9lulas de la capa basal podr\u00eda aportar las se\u00f1ales intracelulares necesarias para el desarrollo de la apoptosis y la acant\u00f3lisis.<\/p>\n<p>&nbsp;<\/p>\n<h3>Datos acad\u00e9micos de la tesis doctoral \u00ab<strong>Papel de las isoformas her y la mtor en la acant\u00f3lisis del p\u00e9nfigo vulgar en un modelo murino<\/strong>\u00ab<\/h3>\n<ul>\n<li><strong>T\u00edtulo de la tesis:<\/strong>\u00a0 Papel de las isoformas her y la mtor en la acant\u00f3lisis del p\u00e9nfigo vulgar en un modelo murino <\/li>\n<li><strong>Autor:<\/strong>\u00a0 Maider Pretel Irazabal <\/li>\n<li><strong>Universidad:<\/strong>\u00a0 Navarra<\/li>\n<li><strong>Fecha de lectura de la tesis:<\/strong>\u00a0 04\/09\/2009<\/li>\n<\/ul>\n<p>&nbsp;<\/p>\n<h3>Direcci\u00f3n y tribunal<\/h3>\n<ul>\n<li><strong>Director de la tesis<\/strong>\n<ul>\n<li>Agustin Espa\u00f1a Alonso<\/li>\n<\/ul>\n<\/li>\n<li><strong>Tribunal<\/strong>\n<ul>\n<li>Presidente del tribunal: natalia Mar\u00eda Lopez moratalia <\/li>\n<li>vicente Garc\u00eda-patos briones (vocal)<\/li>\n<li>eduardo Fonseca capdevila (vocal)<\/li>\n<li>pablo de Unamuno p\u00e9rez (vocal)<\/li>\n<\/ul>\n<\/li>\n<\/ul>\n<p>&nbsp;<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Tesis doctoral de Maider Pretel Irazabal El p\u00e9nfigo vulgar (pv) es una enfermedad ampollosa autoinmune que afecta a piel y [&hellip;]<\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"site-sidebar-layout":"default","site-content-layout":"","ast-site-content-layout":"","site-content-style":"default","site-sidebar-style":"default","ast-global-header-display":"","ast-banner-title-visibility":"","ast-main-header-display":"","ast-hfb-above-header-display":"","ast-hfb-below-header-display":"","ast-hfb-mobile-header-display":"","site-post-title":"","ast-breadcrumbs-content":"","ast-featured-img":"","footer-sml-layout":"","theme-transparent-header-meta":"","adv-header-id-meta":"","stick-header-meta":"","header-above-stick-meta":"","header-main-stick-meta":"","header-below-stick-meta":"","astra-migrate-meta-layouts":"default","ast-page-background-enabled":"default","ast-page-background-meta":{"desktop":{"background-color":"var(--ast-global-color-4)","background-image":"","background-repeat":"repeat","background-position":"center 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