Reversal of the Transcriptome by Prostaglandin E2 during Myofibroblast Dedifferentiation.

Myofibroblasts, the major effector cells in pathologic fibrosis, derive from the differentiation of fibroblasts driven by mediators such as transforming growth factor-β1 (TGF-β1) and biomechanical signals. Although the myofibroblast has traditionally been considered a terminally differentiated cell, the lipid mediator prostaglandin E2 (PGE2) has been shown to not only prevent but also reverse myofibroblast differentiation, as characterized by the ability of PGE2 to diminish expression of collagen I and α-smooth muscle actin in established myofibroblasts. Here, we use microarrays to examine the extent of transcriptomic changes that occur during TGF-β1-induced differentiation and PGE2-induced dedifferentiation of myofibroblasts.

Antileukotriene agents for the treatment of lung disease.

Leukotrienes (LTs) C4, D4, and E4, collectively termed cysteinyl LTs (cysLTs), are lipid mediators formed by the 5-lipoxygenase (5-LO) pathway of arachidonic acid metabolism. Originally recognized for their potent bronchoconstrictor actions, they were subsequently determined also to promote inflammation, microvascular permeability, and mucus secretion. These actions that are so central to asthma pathophysiology are mediated to a significant extent by ligation of the cysLT receptor 1 (CysLT1).

Reversal of myofibroblast differentiation by prostaglandin E(2).

Differentiation of fibroblasts into α-smooth muscle actin (SMA)-expressing myofibroblasts represents a critical step in the pathogenesis of fibrotic disorders, and is generally regarded as irreversible. Prostaglandin E2 (PGE2) has been shown to prevent multiple aspects of fibroblast activation, including the differentiation of fibroblasts to myofibroblasts. Here, we investigated its ability to reverse this differentiated phenotype.