Cell Stem Cell
Volume 20, Issue 2, 2 February 2017, Pages 261-273.e3
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Article
Two-Way Conversion between Lipogenic and Myogenic Fibroblastic Phenotypes Marks the Progression and Resolution of Lung Fibrosis

https://doi.org/10.1016/j.stem.2016.10.004Get rights and content
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Highlights

  • Fate mapping was used to investigate the origin and fate of activated myofibroblasts

  • Lipofibroblasts are precursors for activated myofibroblasts in lung fibrosis

  • Activated myofibroblasts dedifferentiate to lipofibroblasts after recovery

  • PPARγ activation inhibits lipofibroblast-to-myofibroblast transdifferentiation

Summary

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.

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