{"id":101888,"date":"2018-03-11T10:23:52","date_gmt":"2018-03-11T10:23:52","guid":{"rendered":"https:\/\/www.deberes.net\/tesis\/sin-categoria\/angiotensina-ii-y-gremlin-activan-la-via-smad-durante-la-transicion-epitelio-mesenquimal-un-mecanismo-basico-de-progresion-de-dano-renal\/"},"modified":"2018-03-11T10:23:52","modified_gmt":"2018-03-11T10:23:52","slug":"angiotensina-ii-y-gremlin-activan-la-via-smad-durante-la-transicion-epitelio-mesenquimal-un-mecanismo-basico-de-progresion-de-dano-renal","status":"publish","type":"post","link":"https:\/\/www.deberes.net\/tesis\/medicina-interna\/angiotensina-ii-y-gremlin-activan-la-via-smad-durante-la-transicion-epitelio-mesenquimal-un-mecanismo-basico-de-progresion-de-dano-renal\/","title":{"rendered":"Angiotensina ii y gremlin activan la via smad durante la transicion epitelio-mesenquimal, un mecanismo basico de progresion de da\u00f1o renal."},"content":{"rendered":"<h2>Tesis doctoral de <strong> Gisselle Carvajal Gonzalez <\/strong><\/h2>\n<p>La transici\u00f3n epitelio-mesenquimal (tem) es un proceso que contribuye de forma importante a la fibrosis renal. Entre los factores implicados en la progresi\u00f3n del da\u00f1o renal, destaca angiotensina ii (angii) como un elemento clave en la fibrosis. De hecho, los f\u00e1rmacos que bloquean angii son una de las mejores estrategias terap\u00e9uticas actuales en patolog\u00eda renal. El objetivo de esta tesis ha sido investigar los mecanismos moleculares y mediadores implicados en la tem. Para ello se han realizado estudios in vitro, in vivo y en biopsias de pacientes, utilizando t\u00e9cnicas de biolog\u00eda molecular y bioqu\u00edmica. Los resultados demuestran que angii induce tem en el ri\u00f1\u00f3n a trav\u00e9s de la activaci\u00f3n directa, independiente de tgf-\u00edY, de la v\u00eda smad. La regulaci\u00f3n de este proceso es compleja e implica la activaci\u00f3n de otros sistemas de se\u00f1alizaci\u00f3n intracelular (como mapk y rhoa\/rock), y la s\u00edntesis end\u00f3gena de mediadores profibr\u00f3ticos, como tgf-\u00edY y ctgf. En conjunto, estos datos sugieren que el bloqueo de la activaci\u00f3n de smad o de la s\u00edntesis end\u00f3gena de ctgf son dos potenciales dianas terap\u00e9uticas en fibrosis renal. Adem\u00e1s, explican los efectos \u00f3rgano-protectores del bloqueo de angii. El estudio de biopsias de pacientes con diversas glomerulopat\u00edas progresivas mostr\u00f3 sobre-expresi\u00f3n de gremlin en \u00e1reas de fibrosis t\u00fabulo-intersticial, co-localizado con tgf-\u00edY, smad activado y marcadores de tem. Factores claves en el da\u00f1o renal, como angii y tgf-\u00edY, regulan la expresi\u00f3n renal de gremlin. en estudios in vitro, gremlin induce cambios t\u00edpicos de tem, a trav\u00e9s de la activaci\u00f3n de la ruta tgf- \u00edY\/smad. Estos datos sugieren que gremlin puede ser considerado como un nuevo mediador profibr\u00f3tico, y ampl\u00edan los conocimientos sobre los procesos moleculares implicados en la fibrosis renal y sugieren nuevas dianas terap\u00e9uticas para las enfermedades renales cr\u00f3nicas. _________ __ summary epithelial-mesenchymal transition (emt) is an important process that contributes to renal fibrosis. Among the factors involved in the progression of renal damage, angiotensin ii (angii) highlights as inducer of fibrosis. Drugs that block angii actions are one of the best treatments to slow the progression of kidney diseases. The aim of this thesis was to investigate the molecular mechanisms and mediators involved in emt. For this purpose, different approaches were done: in vitro, in vivo and in biopsies studies, using various techniques of molecular biology and biochemistry. The results presented in this study show that angii induces emt in the kidney through direct activation of the smad pathway, independently of tgf-\u00edY. The regulation of this process is complex and involves the activation of other intracellular signaling systems (such as mapk and rhoa\/rock), and endogenous synthesis of profibrotic mediators such as tgf-\u00edY and ctgf. Taken together, these data show that inhibition of smad pathway and endogenous synthesis of ctgf could be good therapeutic strategies against renal fibrosis. in addition, these findings explain the renoprotective effect of drugs that block angii by acting at the cellular level. The study of biopsies from patients with several progressive glomerulopathies showed over-expression of gremlin in areas of tubulointerstitial fibrosis in co-localization with tgf-\u00edY, smad activation and emt markers. Gremlin is regulated in the kidney by key factors in renal damage, such as angii and tgf-\u00edY. Our in vitro studies demonstrated that gremlin induces typical changes of emt through activation of tgf-\u00edY\/smad pathway. These data suggest that gremlin can be considered as a new mediator of fibrosis. These results extend the knowledge about the molecular processes involved in renal fibrosis and suggest new therapeutic targets for chronic kidney disease.<\/p>\n<p>&nbsp;<\/p>\n<h3>Datos acad\u00e9micos de la tesis doctoral \u00ab<strong>Angiotensina ii y gremlin activan la via smad durante la transicion epitelio-mesenquimal, un mecanismo basico de progresion de da\u00f1o renal.<\/strong>\u00ab<\/h3>\n<ul>\n<li><strong>T\u00edtulo de la tesis:<\/strong>\u00a0 Angiotensina ii y gremlin activan la via smad durante la transicion epitelio-mesenquimal, un mecanismo basico de progresion de da\u00f1o renal. <\/li>\n<li><strong>Autor:<\/strong>\u00a0 Gisselle Carvajal Gonzalez <\/li>\n<li><strong>Universidad:<\/strong>\u00a0 Aut\u00f3noma de Madrid<\/li>\n<li><strong>Fecha de lectura de la tesis:<\/strong>\u00a0 21\/06\/2010<\/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 Egido De Los Rios<\/li>\n<\/ul>\n<\/li>\n<li><strong>Tribunal<\/strong>\n<ul>\n<li>Presidente del tribunal: sergio Mezzano abedrapo <\/li>\n<li>concepci\u00f3n Peir\u00f3 vallejo (vocal)<\/li>\n<li>vanesa Esteban v\u00e1zquez (vocal)<\/li>\n<li>adrian mario Ramos cortassa (vocal)<\/li>\n<\/ul>\n<\/li>\n<\/ul>\n<p>&nbsp;<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Tesis doctoral de Gisselle Carvajal Gonzalez La transici\u00f3n epitelio-mesenquimal (tem) es un proceso que contribuye de forma importante a la 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