Inhibidores de la MEK 1/2 para el tratamiento de la fibrosis peritoneal

[EN] Drugs useful in the prevention and treatment of fibrosis of the peritoneal membrane (peritoneal opacification, tanned peritoneum syndrome, mural fibrosis and sclerosing peritonitis syndrome), which arises as a consequence of long-term peritoneal dialysis, method for selecting such dmgs and method for collecting data that are useful in the diagnosis of said disease.[ES] Fármacos útiles en la prevención y tratamiento de la fibrosis de la membrana peritoneal (opacificación peritoneal, síndrome del peritoneo bronceado, fibrosis mural y síndrome de peritonitis esclerosante) que se produce como consecuencia de una diálisis peritoneal a largo plazo, método de selección de estos fármacos, y método para la recolección de datos útiles en el diagnóstico de dicha enfermedad.Peer reviewedCentro Nacional de Investigaciones Cardiovasculares (CNIC), Consejo Superior de Investigaciones Científicas (España)A1 Solicitud de patentes con informe sobre el estado de la técnic

Uso de inhibidores de tak1 en la prevención y tratamiento del fracaso de la membrana peritoneal

[EN] The invention relates to the use of TAKl inhibitors for the preparation of a drug for the prevention and treatment of peritoneal membrane failure, said use preventing and reversing the mesenchymal-epithelial transition experienced by the mesothelial cells of the peritoneum during peritoneal dialysis treatment. In addition, the invention relates to the use of a TAKl expression product or of its activity as a biomarker for determining peritoneal fibrosis. The invention further relates to the method for obtaining data that can be used in the diagnosis and/or prognosis of peritoneal fibrosis and to a method for predicting the progression ofperitoneal fibrosis. The invention also relates to the use of a kit comprising the sequence that codes for TAKl or the protein for the diagnosis of peritoneal fibrosis.[ES] La presente invención se refiere al uso de inhibidores de TAKl para la preparación de un medicamento para la prevención y tratamiento del fracaso de la membrana peritoneal. Donde dicho uso previene y revierte la transición epitelio mesénquima que sufren las células mesoteliales del peritoneo durante el tratamiento de diálisis peritoneal. También, al uso de un producto de expresión de TAKl o de su actividad como biomarcador para la detenninación de fibrosis peritoneal. Al método de obtención de datos útiles en el diagnóstico y/o pronóstico de la fibrosis peritoneal; un método para predecir la progresión de la fibrosis peritoneal. Así como el uso de un kit que comprende la secuencia que codifica para TAKl o la proteína para el diagnóstico de la fibrosis peritoneal.Peer reviewedCentro Nacional de Investigaciones Cardiovasculares, Consejo Superior de Investigaciones Científicas, Centro de Investigación Biomédica en Red:Enfermedades Hepáticas y DigestivasA2 Solicitud de patente sin informe sobre el estado de la técnic

Phosphorylated filamin A regulates actin-linked caveolae dynamics

Caveolae are relatively stable membrane invaginations that compartmentalize signaling, regulate lipid metabolism and mediate viral entry. Caveolae are closely associated with actin fibers and internalize in response to diverse stimuli. Loss of cell adhesion is known to induce rapid and robust caveolae internalization and trafficking toward a Rab11-positive recycling endosome; however, pathways governing this process are poorly understood. Here, we report that filamin A is required to maintain the F-actin-dependent linear distribution of caveolin-1. High spatiotemporal resolution particle tracking of caveolin-1-GFP vesicles by total internal reflection fluorescence (TIRF) microscopy revealed that FLNa is required for the F-actin-dependent arrest of caveolin-1 vesicles in a confined area and their stable anchorage to the plasma membrane. The linear distribution and anchorage of caveolin-1 vesicles are both required for proper caveolin-1 inwards trafficking. De-adhesion-triggered caveolae inward trafficking towards a recycling endosome is impaired in FLNa-depleted HeLa and FLNa-deficient M2-melanoma cells. Inwards trafficking of caveolin-1 requires both the ability of FLNa to bind actin and cycling PKCα-dependent phosphorylation of FLNa on Ser2152 after cell detachment. © 2011. Published by The Company of Biologists Ltd.Peer Reviewe