Nascent lung organoids reveal epithelium- And bone morphogenetic protein-mediated suppression of fibroblast activation

Qi Tan, Xiao Yin Ma, Wei Liu, Jeffrey A. Meridew, Dakota L. Jones, Andrew J. Haak, Delphine Sicard, Giovanni Ligresti, Daniel J. Tschumperlin

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Reciprocal epithelial-mesenchymal interactions are pivotal in lung development, homeostasis, injury, and repair. Organoids have been used to investigate such interactions, but with a major focus on epithelial responses to mesenchyme and less attention to epithelial effects on mesenchyme. In the present study, we used nascent organoids composed of human and mouse lung epithelial and mesenchymal cells to demonstrate that healthy lung epithelium dramatically represses transcriptional, contractile, and matrix synthetic functions of lung fibroblasts. Repression of fibroblast activation requires signaling via the bone morphogenetic protein (BMP) pathway. BMP signaling is diminished after epithelial injury in vitro and in vivo, and exogenous BMP4 restores fibroblast repression in injured organoids. In contrast, inhibition of BMP signaling in healthy organoids is sufficient to derepress fibroblast matrix synthetic function. Our results reveal potent repression of fibroblast activation by healthy lung epithelium and a novel mechanism by which epithelial loss or injury is intrinsically coupled to mesenchymal activation via loss of repressive BMP signaling.

Original languageEnglish (US)
Pages (from-to)607-619
Number of pages13
JournalAmerican journal of respiratory cell and molecular biology
Volume61
Issue number5
DOIs
StatePublished - Jan 1 2019

Fingerprint

Organoids
Bone Morphogenetic Proteins
Fibroblasts
Epithelium
Chemical activation
Lung
Mesoderm
Wounds and Injuries
Homeostasis
Repair
Epithelial Cells

Keywords

  • Airway
  • Alveolar
  • Coculture
  • Fibrosis
  • Mesenchymal

ASJC Scopus subject areas

  • Molecular Biology
  • Pulmonary and Respiratory Medicine
  • Clinical Biochemistry
  • Cell Biology

Cite this

Nascent lung organoids reveal epithelium- And bone morphogenetic protein-mediated suppression of fibroblast activation. / Tan, Qi; Yin Ma, Xiao; Liu, Wei; Meridew, Jeffrey A.; Jones, Dakota L.; Haak, Andrew J.; Sicard, Delphine; Ligresti, Giovanni; Tschumperlin, Daniel J.

In: American journal of respiratory cell and molecular biology, Vol. 61, No. 5, 01.01.2019, p. 607-619.

Research output: Contribution to journalArticle

Tan, Qi ; Yin Ma, Xiao ; Liu, Wei ; Meridew, Jeffrey A. ; Jones, Dakota L. ; Haak, Andrew J. ; Sicard, Delphine ; Ligresti, Giovanni ; Tschumperlin, Daniel J. / Nascent lung organoids reveal epithelium- And bone morphogenetic protein-mediated suppression of fibroblast activation. In: American journal of respiratory cell and molecular biology. 2019 ; Vol. 61, No. 5. pp. 607-619.
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