{"id":113662,"date":"2018-03-11T10:41:14","date_gmt":"2018-03-11T10:41:14","guid":{"rendered":"https:\/\/www.deberes.net\/tesis\/sin-categoria\/papel-de-la-interaccion-colangiocito-matriz-extracelular-en-la-cistogenesis-de-las-enfermedades-hepaticas-poliqua%c2%adsticas\/"},"modified":"2018-03-11T10:41:14","modified_gmt":"2018-03-11T10:41:14","slug":"papel-de-la-interaccion-colangiocito-matriz-extracelular-en-la-cistogenesis-de-las-enfermedades-hepaticas-poliqua%c2%adsticas","status":"publish","type":"post","link":"https:\/\/www.deberes.net\/tesis\/enzimologia\/papel-de-la-interaccion-colangiocito-matriz-extracelular-en-la-cistogenesis-de-las-enfermedades-hepaticas-poliqua%c2%adsticas\/","title":{"rendered":"Papel de la interacci\u00f3n colangiocito-matriz extracelular en la cistog\u00e9nesis de las enfermedades hep\u00e1ticas poliqu\u00edsticas"},"content":{"rendered":"<h2>Tesis doctoral de <strong> Aura Daniela Urribarri Mar\u00edn <\/strong><\/h2>\n<p>Role of cholangiocyte-extracellular matrix interaction in the cystogenesis of polycystic liver disease  aura daniela urribarri mar\u00edn, laboratory of molecular genetics, division of gene therapy and hepatology, school of medicine and cima of the university of navarra (spain) 2012.  polycystic liver diseases (pclds) are genetic disorders characterized by progressive bile-duct dilatation and\/or cyst development, representing the major cause of morbidity and mortality. We have recently reported that cystogenesis in pclds is consequence of hyper-proliferation, hyper-secretion, and alterations in the mirna expression pattern of cholangiocytes. Here we tested the potential role of cholangiocyte-extracelular matrix interaction in the hepatic cystogenesis of pclds. Microfluorimetric assays revealed that polycystic human cholangiocytes in culture present increased metalloprotease (mmp)-activity compared to normal human cholangiocytes, an event associated with increased mrna levels of different mmps by real-time qpcr. Interleukins 6 and 8 (il6, il8) and estrogens, which are upregulated in the cystic fluid of pcld patients, were found to stimulate the mmp-activity of both normal and polycystic human cholangiocytes in culture. The presence of antibodies against il6 and\/or il8 receptor\/s inhibited the basal mmp-hyperactivity of polycystic human cholangiocytes and did not affect the basal mmp-activity of normal human cholangiocytes. Immunohistochemical staining showed mmp3 overexpression in cystic cholangiocytes from pcld tissues compared to normal human livers, as well as in cystic cholangiocytes from pck rat (animal model of pclds) livers compared to normal rat livers. Marimastat, a synthetic pseudopeptide that inhibit mmp-activity, reduced the mmp-hyperactivity of polycystic human cholangiocytes and inhibited the cystic expansion of pck cholangiocytes grown in a 3-dimentional collagen matrix. Finally, chronic treatment of pck rats with marimastat inhibited hepatic cystogenesis. Conclusion: pclds are associated with cholangiocyte mmp-hyperactivity stimulated by il6, il8, and estrogens. Inhibition of this mmp-hyperactivity with marimastat decreased the hepatic cystogenesis in vitro and in an animal model of pcld, representing a potential therapeutic tool for these diseases.<\/p>\n<p>&nbsp;<\/p>\n<h3>Datos acad\u00e9micos de la tesis doctoral \u00ab<strong>Papel de la interacci\u00f3n colangiocito-matriz extracelular en la cistog\u00e9nesis de las enfermedades hep\u00e1ticas poliqu\u00edsticas<\/strong>\u00ab<\/h3>\n<ul>\n<li><strong>T\u00edtulo de la tesis:<\/strong>\u00a0 Papel de la interacci\u00f3n colangiocito-matriz extracelular en la cistog\u00e9nesis de las enfermedades hep\u00e1ticas poliqu\u00edsticas <\/li>\n<li><strong>Autor:<\/strong>\u00a0 Aura Daniela Urribarri Mar\u00edn <\/li>\n<li><strong>Universidad:<\/strong>\u00a0 Navarra<\/li>\n<li><strong>Fecha de lectura de la tesis:<\/strong>\u00a0 20\/12\/2012<\/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>Jes\u00fas Mar\u00eda Ba\u00f1ales Asurmendi<\/li>\n<\/ul>\n<\/li>\n<li><strong>Tribunal<\/strong>\n<ul>\n<li>Presidente del tribunal: Jes\u00fas m. Prieto valtue\u00f1a <\/li>\n<li>Luis Bujanda fernandez de pierola (vocal)<\/li>\n<li>Marta Rodriguez romero (vocal)<\/li>\n<li>Jos\u00e9 Juan Garcia marin (vocal)<\/li>\n<\/ul>\n<\/li>\n<\/ul>\n<p>&nbsp;<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Tesis doctoral de Aura Daniela Urribarri Mar\u00edn Role of cholangiocyte-extracellular matrix interaction in the cystogenesis of polycystic liver disease aura [&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 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":[36483,9399,955,15231,17749],"tags":[225621,15059,170148,1109,136854,156717],"class_list":["post-113662","post","type-post","status-publish","format-standard","hentry","category-biologia-molecular","category-cultivo-celular","category-enzimologia","category-genetica-molecular","category-navarra","tag-aura-daniela-urribarri-marin","tag-jesus-m-prieto-valtuena","tag-jesus-maria-banales-asurmendi","tag-jose-juan-garcia-marin","tag-luis-bujanda-fernandez-de-pierola","tag-marta-rodriguez-romero"],"_links":{"self":[{"href":"https:\/\/www.deberes.net\/tesis\/wp-json\/wp\/v2\/posts\/113662","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.deberes.net\/tesis\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.deberes.net\/tesis\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.deberes.net\/tesis\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/www.deberes.net\/tesis\/wp-json\/wp\/v2\/comments?post=113662"}],"version-history":[{"count":0,"href":"https:\/\/www.deberes.net\/tesis\/wp-json\/wp\/v2\/posts\/113662\/revisions"}],"wp:attachment":[{"href":"https:\/\/www.deberes.net\/tesis\/wp-json\/wp\/v2\/media?parent=113662"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.deberes.net\/tesis\/wp-json\/wp\/v2\/categories?post=113662"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.deberes.net\/tesis\/wp-json\/wp\/v2\/tags?post=113662"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}