Two-Way Conversion between Lipogenic and Myogenic Fibroblastic Phenotypes Marks the Progression and Resolution of Lung Fibrosis

Idiopathic pulmonary fibrosis (IPF) is a form of progressive interstitial lung disease with unknown etiology. Due to a lack of effective treatment, IPF is associated with a high mortality rate. The hallmark feature of this disease is the accumulation of activated myofibroblasts that excessively deposit extracellular matrix proteins, thus compromising lung architecture and function and hindering gas exchange. Here we investigated the origin of activated myofibroblasts and the molecular mechanisms governing fibrosis formation and resolution. Genetic engineering in mice enables the time-controlled labeling and monitoring of lipogenic or myogenic populations of lung fibroblasts during fibrosis formation and resolution. Our data demonstrate a lipogenic-to-myogenic switch in fibroblastic phenotype during fibrosis formation. Conversely, we observed a myogenic-to-lipogenic switch during fibrosis resolution. Analysis of human lung tissues and primary human lung fibroblasts indicates that this fate switching is involved in IPF pathogenesis, opening potential therapeutic avenues to treat patients.

  • El Agha, E.
  • Moiseenko, A.
  • Kheirollahi, V.
  • De Langhe, S.
  • Crnkovic, S.
  • Kwapiszewska, G.
  • Szibor, M.
  • Kosanovic, D.
  • Schwind, F.
  • Schermuly, R. T.
  • Henneke, I.
  • MacKenzie, B.
  • Quantius, J.
  • Herold, S.
  • Ntokou, A.
  • Ahlbrecht, K.
  • Braun, T.
  • Morty, R. E.
  • Gunther, A.
  • Seeger, W.
  • Bellusci, S.


  • Actins/metabolism
  • Animals
  • *Disease Progression
  • Fibroblast Growth Factor 10/metabolism
  • Fibroblasts/metabolism/*pathology
  • Humans
  • Idiopathic Pulmonary Fibrosis/metabolism/*pathology
  • *Lipogenesis
  • Lung/metabolism/pathology
  • Mice
  • *Muscle Development
  • Myocytes, Smooth Muscle/metabolism/pathology
  • Myofibroblasts/metabolism/pathology
  • PPAR gamma/metabolism
  • Phenotype
  • Signal Transduction
  • Transforming Growth Factor beta1/metabolism
Publication details
DOI: 10.1016/j.stem.2016.10.004
Journal: Cell Stem Cell
Journal: Cell stem cell
Pages: 261-273 e3
Number: 2
Work Type: Original
Access number: 27867035
See publication on PubMed