{"id":8007,"date":"2016-01-25T00:00:00","date_gmt":"2016-01-24T23:00:00","guid":{"rendered":"https:\/\/idibell.cat\/blog\/2016\/01\/25\/descobreixen-un-paper-essencial-per-a-una-via-de-senyalitzacio-cel%e2%80%a2lular-que-regula-etapes-primerenques-de-la-regeneracio-i-cancer-hepatics\/"},"modified":"2020-05-13T19:47:18","modified_gmt":"2020-05-13T17:47:18","slug":"descobreixen-un-paper-essencial-per-a-una-via-de-senyalitzacio-cel%e2%80%a2lular-que-regula-etapes-primerenques-de-la-regeneracio-i-cancer-hepatics","status":"publish","type":"post","link":"https:\/\/idibell.cat\/2016\/01\/descobreixen-un-paper-essencial-per-a-una-via-de-senyalitzacio-cel%e2%80%a2lular-que-regula-etapes-primerenques-de-la-regeneracio-i-cancer-hepatics\/","title":{"rendered":"Descobreixen un paper essencial per a una via de senyalitzaci\u00f3 cel\u2022lular que regula etapes primerenques de la regeneraci\u00f3 i c\u00e0ncer hep\u00e0tics"},"content":{"rendered":"

Un grup d’investigadors liderats per les doctores Isabel Fabregat, de l’lnstitut d’Investigaci\u00f3 Biom\u00e8dica de Bellvitge (IDIBELL), i Ar\u00e1nzazu S\u00e1nchez, de la Universitat Complutense de Madrid, han desenvolupat un model de ratol\u00ed modificat gen\u00e8ticament que permet, per primera vegada, estudiar de forma espec\u00edfica en els hepat\u00f2cits (les c\u00e8l\u00b7lules majorit\u00e0ries del fetge) el paper de l’activitat catal\u00edtica del receptor d’una important via de senyalitzaci\u00f3 cel\u00b7lular: la del factor de creixement epid\u00e8rmic (EGF). El treball, publicat a la prestigiosa revista Hepatology, aporta resultats i conclusions noves al voltant de la implicaci\u00f3 d’aquesta via en patologies hep\u00e0tiques com la hepatocarcinog\u00e8nesis (c\u00e0ncer de fetge), la fibrosi hep\u00e0tica o la inflamaci\u00f3, totes elles altament interessants d’estudiar per la seva rellev\u00e0ncia a nivell cl\u00ednic i pel pron\u00f2stic sovint greu que reben els pacients que les pateixen. El treball s\u2019ha dut a terme en estreta col\u00b7laboraci\u00f3 amb investigadors del CIEMAT i de dos centres del CSIC: el CNB i l\u2019IIB-Alberto Sols, a Madrid, i tamb\u00e9 amb investigadors cl\u00ednics de l\u2019Hospital Universitari de Bellvitge, a Barcelona <\/p>\n

El ratol\u00ed transg\u00e8nic sobre el qual es basen els experiments del treball recentment publicat expressa una forma truncada (sense un domini anomenat tirosina-quinasa) del receptor cel\u00b7lular del factor de creixement EGF (EGFR). Aquest model produeix una atenuaci\u00f3 significativa (per\u00f2 no total) i permanent de la seva via de senyalitzaci\u00f3. A causa de que el control del transg\u00e8n l’exerceix el promotor del gen de l’alb\u00famina, s\u00f3n nom\u00e9s els hepat\u00f2cits d’aquests animals els que expressen la forma mutant del EGFR, un aspecte absolutament nou del model, que proporciona als investigadors una eina \u00fanica per a l’estudi de la import\u00e0ncia d’aquesta via de senyalitzaci\u00f3 en processos fisiopatol\u00f2gics del fetge sense afectar la via en altres tipus cel\u00b7lulars de l’organisme. <\/p>\n

Els resultats obtinguts demostren, d’una banda, que l’activaci\u00f3 de la via de l’EGFR \u00e9s crucial durant els primers estadis de la regeneraci\u00f3 hep\u00e0tica, despr\u00e9s de la resecci\u00f3 quir\u00fargica d’una part important de l’\u00f2rgan. En efecte, els ratolins amb la forma mutada d’aquest receptor mostren una regeneraci\u00f3 del fetge retardada i lenta, una baixa activaci\u00f3 de senyals proliferatives i un predomini dels mecanismes citost\u00e0tics. D’altra banda, el mateix model animal ha perm\u00e8s demostrar per primera vegada que la via de l’EGFR juga un paper molt rellevant en els estadis primaris d’aparici\u00f3 de pren\u00f2duls que donaran lloc a tumors hep\u00e0tics. \u00c9s a dir, que l’atenuaci\u00f3 de la via estudiada causa un important retard en l’aparici\u00f3 de tumors. Sorprenentment, el mecanisme responsable dels efectes observats no t\u00e9 relaci\u00f3 amb la inhibici\u00f3 de la proliferaci\u00f3 de les c\u00e8l\u00b7lules, ni tampoc amb un augment de la seva mort programada, sin\u00f3 que es deu a alteracions en el proc\u00e9s inflamatori de l’\u00f2rgan. En efecte, l’atenuaci\u00f3 de la via de l’EGFR disminueix l’entorn inflamatori que propicia l’aparici\u00f3 de pren\u00f2duls i el posterior desenvolupament dels tumors. \u00c9s aquest \u00faltim resultat el que condueix a pensar que l’\u00fas farmacol\u00f2gic d’inhibidors de la via de l’EGFR podria contribuir no nom\u00e9s a atenuar la inflamaci\u00f3 associada a patologies cr\u00f2niques del fetge, sin\u00f3 tamb\u00e9 a retardar l’aparici\u00f3 de tumors. <\/p>\n

La consecuci\u00f3 del present treball representa un clar exemple de com els aven\u00e7os en biomedicina es nodreixen de l’esfor\u00e7 de coordinar la investigaci\u00f3 b\u00e0sica i els aspectes m\u00e9s cl\u00ednics de les patologies contra les quals s’enfronta la societat. El projecte es du a terme amb finan\u00e7ament del Govern catal\u00e0, espanyol i de la Comunitat Europea (acci\u00f3 ITN-Marie Curie). <\/p>\n

Refer\u00e8ncia de l\u2019article: <\/p>\n

Dissecting the role of epidermal growth factor receptor catalytic activity during liver regeneration and hepatocarcinogenesis.<\/a> L\u00f3pez-Luque J, Caballero-D\u00edaz D, Martinez-Palaci\u00e1n A, Roncero C, Moreno-C\u00e0ceres J, Garc\u00eda-Bravo M, Grueso E, Fern\u00e1ndez A, Crosas-Molist E, Garc\u00eda-\u00c1lvaro M, Addante A, Bertran E, Valverde AM, Gonz\u00e1lez-Rodr\u00edguez \u00c1, Herrera B, Montoliu L, Serrano T, Segovia JC, Fern\u00e1ndez M, Ramos E, S\u00e1nchez A, Fabregat<\/strong> I. Hepatology<\/strong>. 2016 Feb;63(2):604-19. doi: 10.1002\/hep.28134. Epub 2015 Oct 10. PMID: 26313466<\/p>\n","protected":false},"excerpt":{"rendered":"

Fabregat Hepatology<\/p>\n","protected":false},"author":6,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"site-sidebar-layout":"no-sidebar","site-content-layout":"page-builder","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":"default","adv-header-id-meta":"","stick-header-meta":"default","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":"","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"tablet":{"background-color":"","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"mobile":{"background-color":"","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""}},"ast-content-background-meta":{"desktop":{"background-color":"var(--ast-global-color-5)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"tablet":{"background-color":"var(--ast-global-color-5)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"mobile":{"background-color":"var(--ast-global-color-5)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""}},"footnotes":""},"categories":[1],"tags":[],"class_list":["post-8007","post","type-post","status-publish","format-standard","hentry","category-sin-categorizar"],"publishpress_future_action":{"enabled":false,"date":"2025-03-02 10:04:00","action":"change-status","newStatus":"draft","terms":[],"taxonomy":"category"},"publishpress_future_workflow_manual_trigger":{"enabledWorkflows":[]},"_links":{"self":[{"href":"https:\/\/idibell.cat\/wp-json\/wp\/v2\/posts\/8007","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/idibell.cat\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/idibell.cat\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/idibell.cat\/wp-json\/wp\/v2\/users\/6"}],"replies":[{"embeddable":true,"href":"https:\/\/idibell.cat\/wp-json\/wp\/v2\/comments?post=8007"}],"version-history":[{"count":0,"href":"https:\/\/idibell.cat\/wp-json\/wp\/v2\/posts\/8007\/revisions"}],"wp:attachment":[{"href":"https:\/\/idibell.cat\/wp-json\/wp\/v2\/media?parent=8007"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/idibell.cat\/wp-json\/wp\/v2\/categories?post=8007"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/idibell.cat\/wp-json\/wp\/v2\/tags?post=8007"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}