Out of Tune: Fibroblasts Turn Fibrotic When They Lack a FENDRR

Idiopathic pulmonary fibrosis (IPF) is a progressive and incurable disease. Patients have a mean life expectancy of 3-5 years after diagnosis. IPF is characterized by widespread remodeling of lung tissue, with excessive deposits of collagen and fibronectin in the extracellular matrix (ECM) and pockets of fibroticfoci. Lung function and gas exchange are significantly impaired by the loss of alveolar space and increased tissue stiffness. In fibrotic disease, unchecked signaling by TGF-p (transforming growth factor-p) and other profibrotic cytokines pushes fibroblasts to become contractile myofibroblasts expressing ACTA2, large amounts of collagen, and other ECM components needed to drive tissue remodeling and disease. Therefore, to identify novel strategies to combat IPF, it is vital to understand the molecular mechanisms involved in fibroblast-to-myofibroblast differentiation and excessive ECM production. In this issue of the Journal, Huang and colleagues report on novel roles for the long noncoding RNA (IncRNA) FENDRR (fetal-lethal noncoding developmental regulatory RNA) in controlling the fibrotic phenotype of lung fibroblasts.