UNASSIGNED: In the infarcted myocardium, necrotic cardiomyocytes activate innate immune pathways, stimulating pro-inflammatory signaling cascades. Although @entity32 plays an important role in clearance of the @entity1188 from dead cells and matrix debris, repair of the infarcted heart requires timely activation of signals that negatively regulate the innate immune response, limiting @entity130 . We have previously demonstrated that @entity14003 , a member of the @entity4101 family that suppresses toll-like receptor/interleukin-1 signaling, is upregulated in the infarcted heart in both macrophages and fibroblasts, and restrains pro-inflammatory activation attenuating adverse remodeling. Although @entity14003 is known to suppress inflammatory activation of macrophages, its role in fibroblasts remains unknown. Our current investigation examines the effects of @entity14003 on fibroblast phenotype and function. In vitro, @entity14003 null cardiac fibroblasts have impaired capacity to contract free-floating collagen pads. @entity14003 loss reduces transforming growth factor (TGF)-b-mediated a-smooth muscle actin ( @entity1970 ) expression. @entity14003 deficient cardiac fibroblasts exhibit a modest reduction in @entity2533 -stimulated Smad activation and increased expression of the @entity1970 repressor, Y-box binding protein (YB)-1. In a model of non-reperfused @entity583 , @entity14003 absence does not affect collagen content and myofibroblast density in the @entity1188 , but increases YB-1 levels and is associated with attenuated @entity1970 expression in isolated @entity1188 . Our findings suggest that, in addition to its role in restraining @entity32 following reperfused @entity1188 , @entity14003 may also contribute to myofibroblast conversion.

The role of Interleukin Receptor Associated Kinase ( @entity4101 )-M in regulation of myofibroblast phenotype in vitro, and in an experimental model of non-reperfused XXXX .

@entity32 :: ('MESH:D007249', 'Disease') :: ['inflammation'] @entity1970 :: ('58', 'Gene') :: ['a-SMA'] @entity4101 :: ('3654', 'Gene') :: ['IRAK'] @entity1188 :: ('MESH:D007238', 'Disease') :: ['infarcted and remodeling myocardium', 'infarct myofibroblasts', 'infarct', 'infarction'] @entity14003 :: ('11213', 'Gene') :: ['Interleukin receptor-associated kinase (IRAK)-M', 'IRAK-M'] @entity2533 :: ('7040', 'Gene') :: ['TGF-b'] @entity583 :: ('MESH:D009203', 'Disease') :: ['myocardial infarction'] @entity130 :: ('MESH:D014947', 'Disease') :: ['inflammatory injury']
@entity583 :: (MESH:D009203,Disease) :: ['myocardial infarction']
