Investigadors de l’Institut d\u2019Investigaci\u00f3 Biom\u00e8dica de Bellvitge (IDIBELL) han liderat un estudi publicat a PLoS One que demostra que la cancel\u00b7laci\u00f3 d’un membre de la fam\u00edlia d’enzims NADPH oxidases, NOX4, juga un important paper en fibrosi hep\u00e0tica.<\/p>\n
La recerca parteix de l’estudi de la funci\u00f3 d’una citoquina, anomenada factor de creixement transformant tipus beta (TGF-beta), en la fisiopatologia del fetge, que \u00e9s una de les principals l\u00ednies de recerca del grup de claus biol\u00f2giques del fenotip invasiu i metast\u00e0tic de l’IDIBELL, dirigit per Isabel Fabregat.<\/p>\n
Aquest treball est\u00e0 relacionat amb els processos de fibrosi hep\u00e0tica. Es tracta d’una patologia en la qual t\u00e9 lloc una sobreproducci\u00f3 de prote\u00efnes de matriu extracel\u00b7lular en el teixit hep\u00e0tic. Durant la fibrosi, els nivells del TGF-beta augmenten i es produeix una activaci\u00f3 de les c\u00e8l\u00b7lules productores de matriu extracel\u00b7lular i altres possibles fen\u00f2mens que condueixen a la mort dels hepat\u00f2cits.<\/p>\n
Dues cares<\/strong><\/p>\n El TGF-beta \u00e9s una citocina molt complexa. D’una banda, \u00e9s un destacat supressor tumoral en estadis primerencs de formaci\u00f3 de tumors. No obstant aix\u00f2, les c\u00e8l\u00b7lules s’adapten per escapar als senyals inhibidors del creixement i, en aquestes condicions, el TGF-beta \u00e9s capa\u00e7 de potenciar la progressi\u00f3 tumoral contribuint a la met\u00e0stasi.<\/p>\n L’estudi publicat a PloS One part d’una col\u00b7laboraci\u00f3 entre l’IDIBELL i l’Institut d’Investigaci\u00f3 de C\u00e0ncer de la Medical University of Vienna (\u00c0ustria), del grup de recerca de Wolfgang Mikulits, coautor de l’estudi, que han aportat models cel\u00b7lulars i animals. L’an\u00e0lisi en mostres de pacients ha estat possible gr\u00e0cies a la col\u00b7laboraci\u00f3 amb l’Hospital Universitari Fundaci\u00f3 Alcorc\u00f3n i la Universitat Complutense de Madrid.<\/p>\n L’objectiu del treball era analitzar rutes per sota del TGF-beta, \u00e9s a dir, les vies indu\u00efdes per aquesta citoquina que puguin ser responsables del proc\u00e9s que d\u00f3na lloc a l’aparici\u00f3 de fibrosi, de l’activaci\u00f3 de les c\u00e8l\u00b7lules productores de matriu extracel\u00b7lular i de la mort dels hepat\u00f2cits.<\/p>\n Diversos estudis previs han demostrat, tant in vitro com in vivo, que seria possible inhibir el TGF-beta per tal de disminuir la fibrosi. No obstant aix\u00f2, el TGF-beta \u00e9s un supressor tumoral. Si s’administra un f\u00e0rmac anti TGF-beta a persones que estan patint un proc\u00e9s de fibrosi hep\u00e0tica es corre el risc d’eliminar un potencial factor de supressi\u00f3 tumoral, “i aix\u00f2 \u00e9s molt important en un proc\u00e9s de fibrosi, que indueix un dany cr\u00f2nic en el fetge i que pot derivar en un carcinoma hep\u00e0tic. Per aix\u00f2, en aquesta situaci\u00f3, l’administraci\u00f3 d’un f\u00e0rmac que \u00e9s un inhibidor d’un factor supressor podria contribuir a una major probabilitat d’aparici\u00f3 de tumors “, comenta la Dra. Fabregat.<\/p>\n Diversos laboratoris estan estudiant les vies per sota del TGF-beta que mitjan\u00e7ant el proc\u00e9s fibr\u00f2tic, per poder mantenir altres vies indu\u00efdes pel TGF-beta que inhibeixin la formaci\u00f3 del tumor. El grup d’investigaci\u00f3 ha demostrat que un membre d’una fam\u00edlia d’enzims implicats en processos d’oxidaci\u00f3, la NOX4, que actua en la via del TGF-beta, juga un important paper en la fibrosi, tant en in vivo, en models experimentals de fibrosi de ratol\u00ed, com in vitro, amb c\u00e8l\u00b7lules en cultiu. “Cancel\u00b7lant NOX4 es preveu tant l’activaci\u00f3 de les c\u00e8l\u00b7lules productores de matriu extracel\u00b7lular com la mort dels hepat\u00f2cits”, conclou la investigadora de l’IDIBELL.<\/p>\n Aplicacions m\u00e8diques<\/strong><\/p>\n El treball tamb\u00e9 demostra que els nivells de NOX4 s\u00f3n molt alts en mostres de pacients en diferents estadis de fibrosi provocada per infecci\u00f3 amb virus d’hepatitis C. Actualment hi ha al mercat inhibidors per NOX4, de manera que l’estudi indica la seva potencialitat cl\u00ednica i explica com podrien actuar si s’empren com a tractament en pacients amb fibrosi hep\u00e0tica.<\/p>\n <\/p>\n Refer\u00e8ncia de l\u2019article<\/strong><\/p>\n Sancho P, Mainez J, Crosas-Molist E, Roncero C, Fern\u00e1ndez-Rodriguez CM, Pinedo F, Huber H, Eferl R, Mikulits W, Fabregat I.NADPH Oxidase NOX4 Mediates Stellate Cell Activation and Hepatocyte Cell Death during Liver Fibrosis Development. PLoS One. 2012; 7(9):e45285. doi: 10.1371\/journal.pone.0045285. Epub 2012 Sep 26.<\/p>\n","protected":false},"excerpt":{"rendered":" Investigadors de l’Institut d\u2019Investigaci\u00f3 Biom\u00e8dica de Bellvitge (IDIBELL) han liderat un estudi publicat a PLoS One que demostra que la cancel\u00b7laci\u00f3 d’un membre de la fam\u00edlia d’enzims NADPH oxidases, NOX4, juga un important paper en fibrosi hep\u00e0tica. La recerca parteix de l’estudi de la funci\u00f3 d’una citoquina, anomenada factor de creixement transformant tipus beta (TGF-beta), […]<\/p>\n","protected":false},"author":6,"featured_media":20839,"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-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-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-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-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-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-gradient":""}},"footnotes":""},"categories":[332,447,360],"tags":[],"publishpress_future_action":{"enabled":false,"date":"2024-05-04 11:21:13","action":"change-status","newStatus":"draft","terms":[],"taxonomy":"category"},"_links":{"self":[{"href":"https:\/\/idibell.cat\/wp-json\/wp\/v2\/posts\/9442"}],"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=9442"}],"version-history":[{"count":2,"href":"https:\/\/idibell.cat\/wp-json\/wp\/v2\/posts\/9442\/revisions"}],"predecessor-version":[{"id":20841,"href":"https:\/\/idibell.cat\/wp-json\/wp\/v2\/posts\/9442\/revisions\/20841"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/idibell.cat\/wp-json\/wp\/v2\/media\/20839"}],"wp:attachment":[{"href":"https:\/\/idibell.cat\/wp-json\/wp\/v2\/media?parent=9442"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/idibell.cat\/wp-json\/wp\/v2\/categories?post=9442"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/idibell.cat\/wp-json\/wp\/v2\/tags?post=9442"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}