{"id":80297,"date":"2020-12-10T12:08:40","date_gmt":"2020-12-10T11:08:40","guid":{"rendered":"http:\/\/ibecbarcelona.eu\/?p=80297"},"modified":"2021-02-04T13:05:46","modified_gmt":"2021-02-04T12:05:46","slug":"un-estudi-internacional-coliderat-per-libec-identifica-els-gens-que-actuen-com-a-protectors-contra-les-malalties-renals","status":"publish","type":"post","link":"https:\/\/ibecbarcelona.eu\/ca\/un-estudi-internacional-coliderat-per-libec-identifica-els-gens-que-actuen-com-a-protectors-contra-les-malalties-renals\/","title":{"rendered":"Un estudi internacional coliderat per l’IBEC identifica els gens que actuen com a protectors contra les malalties renals"},"content":{"rendered":"

A l’estudi, publicat avui a la revista <\/span>Cell<\/span><\/i>\u00a0<\/span><\/i>Metabolism<\/span><\/i>, tamb\u00e9 ha demostrat, en models animals, que \u00e9s possible revertir aquesta defici\u00e8ncia.<\/span>\u00a0<\/span><\/p>\n

La malaltia renal cr\u00f2nica afecta a m\u00e9s de 697 milions de persones a tot el m\u00f3n. En total, s’estima que cada any moren<\/span>\u00a0<\/span>1.2<\/span>\u00a0<\/span>milions de persones a causa d’aquesta malaltia, la qual cosa representa gaireb\u00e9 el 5% de totes les morts anuals a escala mundial. Malgrat l’enorme c\u00e0rrega econ\u00f2mica i personal que aix\u00f2 comporta, fins ara<\/span>\u00a0<\/span>es desconeixien quins eren els mecanismes biol\u00f2gics darrere d’aquesta afecci\u00f3, a causa de la complexitat estructural i funcional del rony\u00f3.<\/span>\u00a0<\/span><\/p>\n

En<\/span>\u00a0un estudi publicat avui a la prestigiosa revista\u00a0<\/span>Cell<\/span><\/i>\u00a0<\/span><\/i>Metabolism<\/span><\/i>, investigadors de l’Institut de<\/span>\u00a0<\/span>Bioenginyeria<\/span>\u00a0<\/span>de Catalunya (IBEC), liderats per la Dra. N\u00faria Montserrat, en col\u00b7laboraci\u00f3 amb investi<\/span>gadors de la Universitat de\u00a0Pen<\/span>n<\/span>silv\u00e0nia\u00a0i de l’Institut de Ci\u00e8ncia i Tecnologia de<\/span>\u00a0G<\/span>wangju, han identificat els gens responsables de la malaltia renal cr\u00f2nica i han demostrat que \u00e9s possible revertir aquesta defici\u00e8ncia, obrint aix\u00ed una possible ruta terap\u00e8utica contra el mal renal.<\/span>\u00a0<\/span><\/p>\n

Fent \u00fas de t\u00e8cniques innovadores com la seq\u00fcenciaci\u00f3 d’ARN<\/span>\u00a0<\/span>a\u00a0<\/span>escala<\/span>\u00a0de<\/span>\u00a0<\/span>c\u00e8l\u00b7lula individual, els investigadors van desxifrar el paper crucial que exerceixen els gens del metabolisme lip\u00eddic a l’hora de protegir enfront de la insufici\u00e8ncia renal cr\u00f2nica. Per a aix\u00f2, les an\u00e0lisis es van realitzar amb models animals i amb<\/span>\u00a0<\/span>mini<\/span>r<\/span>ronyon<\/span>s<\/span>\u00a0<\/span>humans, on els resultats es van validar utilitzant gaireb\u00e9 un centenar de mostres de pacients.<\/span>\u00a0<\/span><\/p>\n

En adults sans, cadascun dels nostres ronyons cont\u00e9 una mitjana<\/span>\u00a0<\/span>d’1.5<\/span>\u00a0<\/span>milions de nefrones, les unitats funcionals b\u00e0siques del rony\u00f3 que filtren constantment els productes de deixalla de la sang. Entre les diferents c\u00e8l\u00b7lules que conformen aquestes unitats de filtraci\u00f3, les c\u00e8l\u00b7lules epitelials del t\u00fabul proximal de la nefrona s\u00f3n les encarregades de realitzar la reabsorci\u00f3 d’aigua i soluts, representant el 90% del total de la massa renal. En gaireb\u00e9 tots els casos de malaltia renal cr\u00f2nica, es produeix un mal en aquestes c\u00e8l\u00b7lules, per\u00f2 fins ara, no se sabia quins mecanismes cel\u00b7lulars eren els responsables de tal disfunci\u00f3.<\/span>\u00a0<\/span><\/p>\n

Mitjan\u00e7ant la seq\u00fcenciaci\u00f3 de l’ARN d<\/span>e cadascuna<\/span>\u00a0<\/span>de<\/span>l<\/span>s<\/span>\u00a0milers<\/span>\u00a0<\/span>de c\u00e8l\u00b7lules presents\u00a0<\/span>a<\/span>l rony\u00f3, els investigadors van observar, per primera vegada, difer\u00e8ncies importants entre les c\u00e8l\u00b7lules sanes i malaltes del t\u00fabul proximal. En concret,\u00a0<\/span>a<\/span>ls ronyons de ratolins amb malaltia renal cr\u00f2nica, van detectar que una major proporci\u00f3 de les c\u00e8l\u00b7lules del t\u00fabul proximal presentaven una signatura molecular diferent de l’oposada en els ronyons d’animals sans.<\/span>\u00a0<\/span><\/p>\n

\"\"
Imatge de microsc\u00f2pia confocal d’un\u00a0<\/span>organoide<\/span>\u00a0de rony\u00f3 generat\u00a0<\/span><\/span>in vitro<\/span><\/span>\u00a0a partir de c\u00e8l\u00b7lules mare pluripotents humanes que han estat diferenciades durant<\/span><\/span>\u00a0<\/span><\/span>20<\/span><\/span>\u00a0<\/span><\/span>dies usant cultius tridimensionals. Aquests\u00a0<\/span>organoides<\/span>\u00a0de rony\u00f3 contenen estructures renals que inclouen t\u00fabuls proximals (marcats amb<\/span><\/span>\u00a0<\/span><\/span>LTL, en verd) i\u00a0<\/span>pod\u00f2cits<\/span>\u00a0(que expressen<\/span><\/span>\u00a0<\/span><\/span>PODXL, en vermell)\u00a0<\/span><\/span>que s’assemblen en part a les estructures renals del rony\u00f3 hum\u00e0.<\/span><\/span>\u00a0<\/span><\/figcaption><\/figure>\n

Davant aquestes observacions, les investigadores d’IBEC<\/span>\u00a0<\/span>van fer un pas m\u00e9s i, utilitzant<\/span>\u00a0<\/span>mini<\/span>r<\/span>ronyon<\/span>s<\/span>\u00a0<\/span>humans, van demostrar que aquests canvis eren deguts a una disminuci\u00f3 en l’expressi\u00f3 d’alguns dels gens que regulen el metabolisme dels l\u00edpids en les c\u00e8l\u00b7lules del t\u00fabul proximal. A m\u00e9s,\u00a0<\/span>\u201c<\/span>gr\u00e0cies a un abordatge multidisciplinari,\u00a0<\/span>i\u00a0<\/span>utilitzant models animals i<\/span>\u00a0<\/span>mini<\/span>r<\/span>ronyon<\/span>s<\/span>\u00a0<\/span>humans que generem mitjan\u00e7ant bioenginyeria a l’IBEC<\/span>, vam\u00a0<\/span>descobri<\/span>r<\/span>\u00a0que, en corregir aquesta defici\u00e8ncia, les c\u00e8l\u00b7lules del t\u00fabul proximal podien recuperar la seva funci\u00f3 en els diferents models d’estudi”, explica la Dra. Montserrat.<\/span>\u00a0<\/span><\/p>\n

T\u00e8cniques d’an\u00e0lisis innovadores: enginyeria gen\u00e8tica i cel\u00b7lular\u00a0<\/strong><\/h2>\n

Combinant la seq\u00fcenciaci\u00f3 d’ARN<\/span>\u00a0<\/span>a\u00a0<\/span>escala<\/span>\u00a0de<\/span>\u00a0<\/span>c\u00e8l\u00b7lula individual, i l’\u00fas de bioenginyeria per a produir<\/span>\u00a0<\/span>mini<\/span>r<\/span>ronyons, va ser possible identificar<\/span>\u00a0<\/span>a\u00a0<\/span>escala<\/span>\u00a0cel\u00b7lular<\/span>\u00a0<\/span>les difer\u00e8ncies clau entre els ronyons sans i malalts.<\/span>\u00a0<\/span><\/p>\n

Els<\/span>\u00a0<\/span>mini<\/span>r<\/span>ronyon<\/span>s<\/span>\u00a0<\/span>humans \u2014tamb\u00e9 denominats\u00a0organoides\u00a0de rony\u00f3\u2014 estan creats mitjan\u00e7ant t\u00e8cniques de<\/span>\u00a0<\/span>bioenginyeria<\/span>\u00a0<\/span>a partir de c\u00e8l\u00b7lules mare humanes, i recullen alguns aspectes de la complexitat d’aquest \u00f2rgan real. El<\/span>\u00a0passat mes d’abril<\/span>, ja van demostrar la seva efic\u00e0cia com a model d’estudi en utilitzar-los per a desxifrar en temps r\u00e8cord com<\/span>\u00a0<\/span>la SARS-Co-V2 interacciona i infecta les c\u00e8l\u00b7lules d’aquests<\/span>\u00a0<\/span>mini-ronyon<\/span>s<\/span>, a m\u00e9s d’identificar una ter\u00e0pia dirigida a reduir la c\u00e0rrega viral.<\/span>\u00a0<\/span><\/p>\n

En aquest estudi<\/span>,<\/span>\u00a0la seq\u00fcenciaci\u00f3 d’ARN<\/span>\u00a0<\/span>a\u00a0<\/span>escala<\/span>\u00a0de<\/span>\u00a0<\/span>c\u00e8l\u00b7lula individual de les mostres dels<\/span>\u00a0<\/span>mini<\/span>r<\/span>ronyon<\/span>s<\/span>\u00a0<\/span>s’ha realitzat\u00a0<\/span>a<\/span>l laboratori del Dr.<\/span>\u00a0<\/span>Felipe<\/span>\u00a0<\/span>Pr\u00f3sper<\/span>\u00a0<\/span>de la Cl\u00ednica Universitat de Navarra i CIM Universitat de Navarra. “El rony\u00f3 t\u00e9 m\u00e9s de 23 tipus de c\u00e8l\u00b7lules diferents”, explica la Dra. Montserrat. “Fa uns anys, era necessari examinar m\u00faltiples mostres per separat per a obtenir la informaci\u00f3, la qual cosa podia comportar anys de treball, ara aquesta mateixa informaci\u00f3 la podem obtenir en pocs dies”, i afegeix: “amb la seq\u00fcenciaci\u00f3 d’ARN de cadascuna de les c\u00e8l\u00b7lules del\u00a0<\/span>rony\u00f3 i utilitzant m\u00faltiples mostres, podem identificar quins gens estan diferencialment expressats en cadascuna de les<\/span>\u00a0<\/span>c\u00e8l\u00b7lules”.<\/span>\u00a0<\/span><\/p>\n

Estudiant aquestes difer\u00e8ncies o, dit d’una altra manera, analitzant la “signatura” de l’expressi\u00f3 de l’ARN de cadascuna d’aquestes c\u00e8l\u00b7lules, els investigadors van identificar que la disfunci\u00f3 del t\u00fabul proximal \u00e9s conseq\u00fc\u00e8ncia de la desregulaci\u00f3 d’una via metab\u00f2lica clau. Espec\u00edficament,\u00a0<\/span>a<\/span>\u00a0les mostres malaltes de ratolins, tamb\u00e9 es va trobar una major proporci\u00f3 de c\u00e8l\u00b7lules immadures. “Se sap que una petita proporci\u00f3 de les c\u00e8l\u00b7lules dels t\u00fabuls proximals del rony\u00f3 presenten un comportament similar al de les c\u00e8l\u00b7lules mare”, assenyala la Dra.<\/span>\u00a0<\/span>Carmen<\/span>\u00a0<\/span>Hurtado<\/span>\u00a0<\/span>del Pou, investigadora de l’IBEC<\/span>\u00a0<\/span>i coautora de l’estudi. “Quan es produeixen danys en el rony\u00f3, el t\u00fabul proximal tendeix a respondre molt r\u00e0pidament, ja que pot restaurar les parts de la nefrona que estan lesionades. No obstant aix\u00f2, durant la malaltia renal cr\u00f2nica, aquestes c\u00e8l\u00b7lules perden la seva capacitat regenerativa”, subscriu la Dra. Montserrat.<\/span>\u00a0<\/span><\/p>\n

El paper protector del metabolisme en el mal renal\u00a0<\/strong><\/h2>\n

Aquest treball ha identificat els gens metab\u00f2lics que es desactiven quan el rony\u00f3 est\u00e0 sotm\u00e8s a un mal cr\u00f2nic, perdent-se la “signatura” sana en les c\u00e8l\u00b7lules del t\u00fabul proximal del rony\u00f3. Per\u00a0<\/span>a\u00a0<\/span>aquesta signatura, el receptor d’estrogen alfa (ESRRa, per les seves sigles en angl\u00e8s) \u00e9s un dels marcadors que t\u00e9 un paper m\u00e9s rellevant. “Aquests gens s\u00f3n especialment importants per a les c\u00e8l\u00b7lules del t\u00fabul proximal, ja que necessiten tenir un metabolisme molt actiu. De fet, despr\u00e9s de les c\u00e8l\u00b7lules\u00a0<\/span>del cor, s\u00f3n aquestes c\u00e8l\u00b7lules<\/span>\u00a0les que tenen el requeriment energ\u00e8tic m\u00e9s gran del nostre cos<\/span>“, explica la Dra. Montserrat.\u00a0<\/span>“Quan l’expressi\u00f3 dels gens que controlen el metabolisme dels l\u00edpids disminueix, el rony\u00f3 perd la seva capacitat de respondre enfront del mal”, afegeix la Dra. Carmen Hurtado del Pou.<\/span>\u00a0<\/span><\/p>\n

Mitjan\u00e7ant la generaci\u00f3 de<\/span>\u00a0<\/span>mini<\/span>r<\/span>ronyon<\/span>s<\/span>, les investigadores d<\/span>e l<\/span>‘IBEC<\/span>\u00a0<\/span>van poder simular condicions de cultiu amb la finalitat de manipular els nivells<\/span>\u00a0<\/span>d<\/span>\u2019<\/span>ESRRa<\/span>\u00a0<\/span>a<\/span>\u00a0les c\u00e8l\u00b7lules d’aquests<\/span>\u00a0<\/span>mini\u00f2rgan<\/span>s. Quan es va tornar a encendre<\/span>\u00a0l\u2019<\/span>ESRRa, el t\u00fabul proximal semblava tornar a recuperar la seva funci\u00f3. Tals observacions es donaven\u00a0<\/span>a<\/span>ls models animals que els col\u00b7laboradors de la Universitat de\u00a0<\/span>Pennsilv\u00e0nia<\/span>\u00a0\u2014els qui fa dos anys ja van publicar, per primera vegada, l’\u00fas de la seq\u00fcenciaci\u00f3 d’ARN<\/span>\u00a0<\/span>a\u00a0<\/span>escala<\/span>\u00a0de<\/span>\u00a0<\/span>c\u00e8l\u00b7lula individual en ronyons de ratolins sans.<\/span>\u00a0<\/span><\/p>\n

Aquest treball demostra que la combinaci\u00f3 de tecnologies emergents, com la seq\u00fcenciaci\u00f3 d’ARN<\/span>\u00a0<\/span>a\u00a0<\/span>escala<\/span>\u00a0<\/span>de<\/span>\u00a0<\/span>c\u00e8l\u00b7lula \u00fanica i els<\/span>\u00a0<\/span>mini\u00f2rgan<\/span>s, poden ser molt avantatjoses a l’hora\u00a0<\/span>d\u2019<\/span>avan\u00e7ar en recerca biom\u00e8dica.<\/span>\u00a0Aquest estudi proposa que, juntament a<\/span>mb<\/span>\u00a0<\/span>l\u2019<\/span>ESRRa, existeixen altres receptors nuclears que poden actuar, en un futur pr\u00f2xim, com a dianes terap\u00e8utiques\u00a0<\/span>p<\/span>er a revertir la malaltia renal cr\u00f2nica.<\/span>\u00a0<\/span><\/p>\n

\"\"<\/p>\n

L’estudi ha estat\u00a0codirigit\u00a0per la Dra. N\u00faria Montserrat,<\/span>\u00a0<\/span>Professora<\/span>\u00a0<\/span>de Recerca<\/span>\u00a0<\/span>ICREA<\/span>\u00a0<\/span>i Investigadora principal del grup “Pluripot\u00e8ncia<\/a><\/span>\u00a0<\/span>per a la regeneraci\u00f3 d’\u00f2rgans” de l’Institut de Bioenginyeria de Catalunya (IBEC), el Dr.<\/span>\u00a0<\/span>Katalin<\/span>\u00a0<\/span>Susztak<\/span>\u00a0<\/span>de la Universitat de\u00a0Pennsilv\u00e0nia\u00a0i el Dr.<\/span>\u00a0<\/span>Jihwan<\/span>\u00a0<\/span>Park<\/span>\u00a0<\/span>de l’Institut de Ci\u00e8ncia i Tecnologia de<\/span>\u00a0<\/span>Gwangju.<\/span>\u00a0<\/span><\/p>\n

N\u00faria Montserrat tamb\u00e9 \u00e9s membre del Centre de Recerca Biom\u00e8dica en Xarxa en Bioeng<\/span>inyeria, Biomaterials i\u00a0Nanomedi<\/span>cina\u00a0(CIBER<\/span>\u00a0<\/span>BBN).<\/span>\u00a0<\/span><\/p>\n

\n
\n

Sobre l’Institut de<\/span><\/b>\u00a0<\/span><\/b>Bioenginyeria<\/span><\/b>\u00a0<\/span><\/b>de Catalunya (IBEC):<\/span><\/b>
\n<\/span>L’Institut de<\/span>\u00a0<\/span>Bioenginyeria<\/span>\u00a0<\/span>de Catalunya (IBEC) \u00e9s un centre\u00a0<\/span>CERCA (Centres de Recerca de Catalunya)<\/span>,\u00a0<\/span>dues vegades reconegut com a Centre d’Excel\u00b7l\u00e8ncia Severo Ochoa, i membre de l’Institut de Ci\u00e8ncia i Tecnologia de Barcelona (BIST). L’IBEC<\/span>\u00a0<\/span>duu a terme recerques multidisciplin\u00e0ries d’excel\u00b7l\u00e8ncia a la frontera entre l’enginyeria i les ci\u00e8ncies de la vida per a generar coneixement, integrant camps com la\u00a0nanomedicina, biof\u00edsica, biotecnologia, enginyeria de teixits i les aplicacions tecnol\u00f2giques de la informaci\u00f3 en el camp de la salut. L’IBEC<\/span>\u00a0<\/span>es va crear en 2005 per la Generalitat de Catalunya, la Universitat de Barcelona (UB) i la Universitat Polit\u00e8cnica de Catalunya (UPC).<\/span>\u00a0<\/span><\/p>\n

\n
\n

Per a m\u00e9s informaci\u00f3 contactar amb:<\/span><\/i>\u00a0<\/span><\/p>\n

\u00c0ngels L\u00f3pez\u00a0<\/span>
\n<\/span>Departament de comunicaci\u00f3 (IBEC)<\/span>
\n<\/span>alopez@ibecbarcelona.eu<\/span><\/a>
\n<\/span><\/p>\n

\u00a0<\/span><\/p>\n","protected":false},"excerpt":{"rendered":"

Investigadores de l’Institut de Bioenginyeria de Catalunya (IBEC), liderades per la Dra.N\u00faria Montserrat, en col\u00b7laboraci\u00f3 amb investigadors internacionals, han identificat els gens que podrien protegir al rony\u00f3 del mal cr\u00f2nic. 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