Referencia

Proc Natl Acad Sci U S A. 2010 Jun 8;107(23):10626-31. Epub 2010 May 24.

Autores

Vanessa Núñeza,1, Daniel Alamedaa,1, Daniel Ricoa,2, Rubén Motab, Pilar Gonzalob, Marta Cedenillaa, Thierry Fischerc, Lisardo Boscád, Christopher K. Glasse, Alicia G. Arroyob, and Mercedes Ricotea,3 Departments of aRegenerative Cardiology and bVascular Biology and Inflammation, Centro Nacional de Investigaciones Cardiovasculares, Madrid 28029, Spain; cDepartment of Immunology and Oncology, Centro Nacional de Biotecnología, Madrid 28049, Spain; dInstituto de Investigaciones Biomédicas “Alberto Sols” (CSIC-UAM), Madrid 28029, Spain; and eDepartment of Medicine, Department of Cellular and Molecular Medicine, University of California,La Jolla, CA 92093 1V.N. and D.A. contributed equally to this work. 2Present address: Structural Biology and Biocomputing Programme, Centro Nacional de Investigaciones Oncológicas, Madrid 28029, Spain. 3To whom correspondence should be addressed. E-mail: This email address is being protected from spambots. You need JavaScript enabled to view it..

Resumen

En nuestro trabajo describimos el papel del receptor X de retinoides (RXR) en la función de los macrófagos durante procesos inflamatorios. RXR es miembro de la superfamilia de los receptores nucleares que son factores de transcripción activados por ligando. Para estudiar la función de RXR en macrófagos generamos un ratón knock-out para RXRα específico de la línea mieloide. Dichos ratones mostraron una disminución en la migración leucocitaria al foco de inflamación en modelos de peritonitis estéril y un incremento en la supervivencia en modelos de sepsis. Todo ello se correlacionó con una reducción en los niveles de las quimioquinas pro-inflamatorias CCL6 y CCL9. Además demostramos que estas quimioquinas están reguladas transcripcionalmente por RXR como homodimero. Nuestros resultados sugieren que RXR es una posible diana terapéutica para el tratamiento de enfermedades inflamatorias.

Descripción

Imagen artículo Julio

REFERENCIA DEL GRUPO Y/O INVESTIGADOR
Los receptores nucleares constituyen una superfamilia de factores de transcripción dependientes de ligando que regulan diferentes aspectos del crecimiento, el desarrollo y la homeostasis. Una de las principales cuestiones en el campo de los receptores nucleares es el descubrimiento de los mecanismos moleculares que median la activación y represión de los genes diana de estos receptores. El objetivo central del laboratorio de la Dra. Mercedes Ricote es elucidar los programas transcripcionales por los cuales estos receptores regulan la expresión génica en macrófagos y como estos patrones de expresión específicos podrían ser modulados para prevenir el desarrollo de enfermedades humanas, tales como obesidad, diabetes y enfermedades cardiovasculares. Para llevar a cabo estos estudios se utiliza una combinación de técnicas de biología molecular/celular, genómica, modelos animales in vivo, específicamente animales knockouts condicionales en macrófagos y tecnología de microarrays. En el trabajo recientemente publicado en Proceedings of the National Academy of Science se establece que el receptor X de retinoides (RXR) desempeña un papel importante en la respuesta innata. El resultado de nuestros experimentos demuestra que RXR es una potencial diana terapéutica para el tratamiento y prevención de la sepsis así como de otras enfermedades inflamatorias crónicas. Otras líneas de investigación del laboratorio exploran el papel de los receptores nucleares en las bases moleculares de la resistencia a la insulina y la aterosclerosis. Mercedes Ricote es investigadora del Centro Nacional de Investigaciones Cardiovasculares (CNIC).

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