Reversal of the Transcriptome by XXXX during Myofibroblast Dedifferentiation.

@entity2533 @entity1421 @entity1 @entity82
UNASSIGNED: Myofibroblasts, the major effector cells in pathologic @entity82 , derive from the differentiation of fibroblasts driven by mediators such as @entity2533 ( @entity2533 ) and biomechanical signals. Although the myofibroblast has traditionally been considered a terminally differentiated cell, the lipid mediator @entity1421 ( @entity1421 ) has been shown to not only prevent but also reverse myofibroblast differentiation, as characterized by the ability of @entity1421 to diminish expression of collagen I and a-smooth muscle actin in established myofibroblasts. Here, we use microarrays to examine the extent of transcriptomic changes that occur during @entity2533 -induced differentiation and @entity1421 -induced dedifferentiation of myofibroblasts. Normal primary @entity1 adult lung fibroblasts were cultured for 24 hours with or without @entity2533 and treated for 48 hours with @entity1421 . Gene expression levels were assessed from total RNA on the Affymetrix U219 microarray. @entity2533 up-regulated 588 genes and down-regulated 689 genes compared with control cells. @entity1421 reversed the expression of 363 (62%) of the @entity2533 -up-regulated genes and 345 (50%) of the @entity2533 -down-regulated genes. Genes up-regulated by @entity2533 and reversed by @entity1421 were enriched in annotations for Cell Adhesion, Contractile Fiber, and Actin Binding, whereas genes down-regulated by @entity2533 but subsequently reversed by @entity1421 were enriched in annotations for Glycoprotein, Polysaccharide Binding, and Regulation of Cell Migration. Surprisingly, the genes whose expression was affected by @entity1421 differed between @entity2533 -induced myofibroblasts and undifferentiated fibroblasts. These data demonstrate the capacity of @entity1421 to effect marked global alterations in the transcriptomic program of differentiated myofibroblasts and emphasize the considerable plasticity of these cells.
