{"id":108019,"date":"2018-03-11T10:32:38","date_gmt":"2018-03-11T10:32:38","guid":{"rendered":""},"modified":"2018-03-11T10:32:38","modified_gmt":"2018-03-11T10:32:38","slug":"estudio-de-la-expresion-genica-de-diversos-componentes-del-sistema-fibrinola%c2%adtico-de-las-metaloproteasas-y-de-la-angiogenesis-en-la-endometriosis-correlacion-de-los-niveles-de-expresion-con-alg","status":"publish","type":"post","link":"https:\/\/www.deberes.net\/tesis\/bioquimica\/estudio-de-la-expresion-genica-de-diversos-componentes-del-sistema-fibrinola%c2%adtico-de-las-metaloproteasas-y-de-la-angiogenesis-en-la-endometriosis-correlacion-de-los-niveles-de-expresion-con-alg\/","title":{"rendered":"Estudio de la expresi\u00f3n g\u00e9nica de diversos componentes del sistema fibrinol\u00edtico, de las metaloproteasas y de la angiog\u00e9nesis en la endometriosis. correlaci\u00f3n de los niveles de expresi\u00f3n con algunos polimorfismos estudiados."},"content":{"rendered":"<h2>Tesis doctoral de <strong> Luis Andr\u00e9s Ram\u00f3n  N\u00fa\u00f1ez <\/strong><\/h2>\n<p>Introducci\u00f3n: la endometriosis, definida como la presencia de tejido endometrial fuera del \u00fatero, es una de las enfermedades ginecol\u00f3gicas benignas m\u00e1s frecuentes. La endometriosis es una entidad multifactorial y polig\u00e9nica en la que tanto factores endometriales como peritoneales, relacionados con los sistemas de activaci\u00f3n del plasmin\u00f3geno (pa) y de las metaloproteasas (mmps) y la angiog\u00e9nesis, pueden estar implicados en esta enfermedad.   objetivo: analizar los niveles de mrna y prote\u00edna de factores angiog\u00e9nicos (factor de crecimiento del endotelio vascular, vegf-a y trombospondina-1, tsp-1) y componentes de los sistemas pa (uroquinasa, upa; inhibidor del pa tipo 1, pai-1) y de las mmps (mmp-3; inhibidor de mmps de tipo 1, timp-1) en tejido endometri\u00f3sico y endometrio de mujeres con y sin endometriosis. Tambi\u00e9n se estudiaron los niveles proteicos de estos componentes en el l\u00edquido peritoneal (lp) de pacientes y controles. Por otra parte, se estudiaron los polimorfismos 4g\/5g del gen del pai-1, 5a\/6a del gen de la mmp-3 y tres polimorfismos funcionales del gen del vegf-a (-460c\/t, +405g\/c y 936c\/t) en pacientes y controles y se analiz\u00f3 la influencia de estos polimorfismos en la expresi\u00f3n de pai-1, mmp-3 y vegf-a en tejido endometrial y lp. Por \u00faltimo, se evalu\u00f3 la influencia del lp sobre la expresi\u00f3n de factores proteol\u00edticos y angiog\u00e9nicos en cultivos de c\u00e9lulas endometriales procedentes de pacientes y controles.   m\u00e9todos: los niveles de mrna se cuantificaron mediante qrt-pcr en tiempo real y los niveles proteicos mediante elisa. El polimorfismo 4g\/5g del gen del pai-1 se evalu\u00f3 mediante pcr con cebadores espec\u00edficos de alelo. El polimorfismo 5a\/6a de la mmp-3 y los polimorfismos del vegf-a se determinaron mediante pcr-rflp. Por \u00faltimo, se aislaron y cultivaron c\u00e9lulas endometriales (de pacientes y controles) y se trataron con lp de pacientes y controles. Posteriormente, se evaluaron los niveles de mrna y prote\u00edna de los factores estudiados.   resultados y conclusiones: el endometrio y el lp de las mujeres con endometriosis mostr\u00f3 unos niveles de upa, mmp-3 y vegf-a superiores a los controles. Este incremento puede facilitar la adhesi\u00f3n del tejido endometrial al peritoneo y ovario, la invasi\u00f3n de la matriz extracelular y la angiog\u00e9nesis, contribuyendo a la formaci\u00f3n de las lesiones endometri\u00f3sicas tempranas. El tejido endometri\u00f3sico ov\u00e1rico mostr\u00f3 unos niveles superiores de pai-1, timp-1 y tsp-1 que el endometrio, lo que podr\u00eda explicar la presencia del quiste endometri\u00f3sico con ausencia de invasi\u00f3n al tejido ov\u00e1rico adyacente.  las frecuencias genot\u00edpicas y al\u00e9licas del polimorfismo 4g\/5g del gen del pai-1 no difieren entre pacientes y controles, aunque los niveles de pai-1, en tejido endometrial y lp de controles, parecen estar asociados con este polimorfismo.  las pacientes mostraron una mayor frecuencia del alelo 936t, del gen del vegf, que los controles. Sin embargo no se encontraron diferencias en la distribuci\u00f3n de frecuencias genot\u00edpicas y al\u00e9licas en los otros dos polimorfismos del vegf-a (-460c\/t, +405g\/c) entre pacientes y controles. Estos hallazgos sugieren que el polimorfismo 936c\/t puede estar asociado con el riesgo de padecer endometriosis, aunque el incremento en los niveles de vegf-a, observado en las mujeres con endometriosis, no parece estar asociado con ninguno de  los polimorfismos estudiados.  por \u00faltimo, el lp de las mujeres con endometriosis indujo un incremento en los niveles de upa y vegf-a en cultivos de c\u00e9lulas endometriales de pacientes y controles. Los mayores niveles de upa y vegf-a se observaron en cultivos de c\u00e9lulas endometriales de pacientes tratados con lp de mujeres con endometriosis. Por tanto, el lp induce, en las c\u00e9lulas endometriales, una mayor expresi\u00f3n de factores proteol\u00edticos y angiog\u00e9nicos que pueden contribuir al desarrollo de las lesiones endometri\u00f3sicas.     introduction: endometriosis, defined as the presence of endometrium outside the uterus, is one of the most frequent benign gynaecological diseases. It is a multifactorial and polygenic entity in which both endometrial and peritoneal factors, related to plasminogen activator and matrix metalloproteinase systems and angiogenesis, can be implicated.  objetive: to analyze mrna and protein levels of angiogenic and proteolytic factors in endometriotic and endometrial tissues from patients and controls. The protein levels were also studied in peritoneal fluid (pf). Pai-1 4g\/5g, mmp-3 5a\/6a and vegf-a -460c\/t, +405g\/c and 936c\/t polymorphisms were evaluated. Finally, the influence of pf on proteolytic and angiogenic factor expression in endometrial cell cultures (eccs) was evaluated.    methods: mrna and protein levels were quantified by real-time qrt-pcr assay and elisa, respectively. Pai-1 4g\/5g polymorphism was determined by allele-specific pcr. Mmp-3 5a\/6a and vegf polymorphisms (-460c\/t, +405g\/c, and 936c\/t) were determined using a pcr-rflp assay. Finally, eccs were treated with pf from patients and controls.   results and conclusions: endometrium and pf from patients showed higher upa, mmp-3 and vegf-a levels than controls. This increase may facilitate the attachment of endometrial tissue to the peritoneum and ovarian surface. This process would lead to the formation of early endometriotic lesions. Ovarian endometrioma had higher pai-1, timp-1 and tsp-1 levels than endometrium, which could explain the finding of one endometrioma without adjacent tissue invasion.   the pai-1 4g\/5g genotypes and allele frequencies did not differ between patients and controls. However, endometrial and peritoneal pai-1 levels seem to be associated with pai-1 4g\/5g polymorphism in controls.  patients showed a higher vegf 936t allele frequency than controls. These findings suggest that the vegf 936c\/t polymorphism may be associated with the risk of endometriosis.  finally, pf induced an increase in upa and vegf-a levels in eccs.  The highest levels were observed in eccs from patients with endometriosis treated with pf from women with endometriosis. So, pf induces a higher expression of proteolytic and angiogenic factors in eecs, which could contribute to the development of endometriotic lesions.<\/p>\n<p>&nbsp;<\/p>\n<h3>Datos acad\u00e9micos de la tesis doctoral \u00ab<strong>Estudio de la expresi\u00f3n g\u00e9nica de diversos componentes del sistema fibrinol\u00edtico, de las metaloproteasas y de la angiog\u00e9nesis en la endometriosis. correlaci\u00f3n de los niveles de expresi\u00f3n con algunos polimorfismos estudiados.<\/strong>\u00ab<\/h3>\n<ul>\n<li><strong>T\u00edtulo de la tesis:<\/strong>\u00a0 Estudio de la expresi\u00f3n g\u00e9nica de diversos componentes del sistema fibrinol\u00edtico, de las metaloproteasas y de la angiog\u00e9nesis en la endometriosis. correlaci\u00f3n de los niveles de expresi\u00f3n con algunos polimorfismos estudiados. <\/li>\n<li><strong>Autor:<\/strong>\u00a0 Luis Andr\u00e9s Ram\u00f3n  N\u00fa\u00f1ez <\/li>\n<li><strong>Universidad:<\/strong>\u00a0 Universitat de val\u00e9ncia (estudi general)<\/li>\n<li><strong>Fecha de lectura de la tesis:<\/strong>\u00a0 15\/04\/2011<\/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>Amparo Estell\u00e9s Cort\u00e9s<\/li>\n<\/ul>\n<\/li>\n<li><strong>Tribunal<\/strong>\n<ul>\n<li>Presidente del tribunal: concepci\u00f3n Abad mazario <\/li>\n<li>pascual Bolufer gilabert (vocal)<\/li>\n<li>edelmiro R\u00e9ganon salvador (vocal)<\/li>\n<li>pilar Sanchez gomez (vocal)<\/li>\n<\/ul>\n<\/li>\n<\/ul>\n<p>&nbsp;<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Tesis doctoral de Luis Andr\u00e9s Ram\u00f3n N\u00fa\u00f1ez Introducci\u00f3n: la endometriosis, definida como la presencia de tejido endometrial fuera del \u00fatero, [&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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