XXXX inhibits the transforming growth factor-b profibrotic action, blocking the signaling mediated by the ETR/TbRI complex in @entity785 dermal fibroblasts.

@entity1 @entity82 @entity19629 @entity2232 @entity13239 @entity1970 @entity2533 @entity11280 @entity792 @entity785
INTRODUCTION: @entity785 ( @entity785 ) is a complex and not fully understood @entity792 associated with @entity82 of multiple organs. The main effector cells, the myofibroblasts, are collagen-producing cells derived from the activation of resting fibroblasts. This process is regulated by a complex repertoire of profibrotic cytokines, and among them @entity2533 ( @entity2533 ) and @entity2232 ( @entity2232 ) play a major role. In this paper we show that @entity2533 and @entity2232 receptors co-operate in myofibroblast activation, and @entity19629 , an @entity2232 receptor antagonist binding @entity2232 receptors, might interfere with both @entity2533 and @entity2232 pathways, preventing myofibroblast differentiation. METHODS: Fibroblasts isolated from healthy controls and @entity785 @entity1 were treated with @entity2533 and @entity2232 and successively analyzed for @entity1970 ( @entity1970 ) and collagen ( @entity13239 ) expression and for the @entity11280 and Mad Related (SMAD) phosphorylation. We further tested the ability of @entity19629 to interfere with these process. Furthermore, we silenced @entity2232 and @entity2232 receptor A expression and evaluated the formation of an @entity2232 / @entity2533 receptor complex by immunoprecitation assay. RESULTS: We showed myofibroblast activation in @entity785 fibroblasts assessing the expression of @entity1970 and @entity13239 , after stimulation with @entity2533 and @entity2232 . @entity19629 interfered with both @entity2232 - and @entity2533 -induced fibroblast activation. To explain this unexpected inhibitory effect of @entity19629 on @entity2533 activity, we silenced @entity2232 expression on @entity785 fibroblasts and co-immunoprecipitated these two receptors, showing the formation of an @entity2232 / @entity2533 receptor complex. CONCLUSIONS: During @entity785 , @entity2232 produced by activated endothelia contributes to myofibroblast activation using @entity2533 machinery via an @entity2232 / @entity2533 receptor complex. @entity19629 interferes with the profibrotic action of @entity2533 , blocking the @entity2232 receptor portion of the @entity2232 / @entity2533 receptor complex.
