Journal article
Nascent Lung Organoids Reveal Epithelium- and Bone Morphogenetic Protein-mediated Suppression of Fibroblast Activation
American journal of respiratory cell and molecular biology, Vol.61(5), pp.607-619
11/01/2019
DOI: 10.1165/rcmb.2018-0390OC
PMCID: PMC6827068
PMID: 31050552
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.
Details
- Title: Subtitle
- Nascent Lung Organoids Reveal Epithelium- and Bone Morphogenetic Protein-mediated Suppression of Fibroblast Activation
- Creators
- Qi Tan - Mayo ClinicXiao Yin Ma - Mayo Clin, Dept Physiol & Biomed Engn, 200 1st St SW, Rochester, MN 55905 USAWei Liu - Mayo ClinicJeffrey A. Meridew - Mayo ClinicDakota L. Jones - Mayo ClinicAndrew J. Haak - Mayo ClinicDelphine Sicard - Mayo ClinicGiovanni Ligresti - Mayo ClinicDaniel J. Tschumperlin - Mayo Clinic
- Resource Type
- Journal article
- Publication Details
- American journal of respiratory cell and molecular biology, Vol.61(5), pp.607-619
- DOI
- 10.1165/rcmb.2018-0390OC
- PMID
- 31050552
- PMCID
- PMC6827068
- NLM abbreviation
- Am J Respir Cell Mol Biol
- ISSN
- 1044-1549
- eISSN
- 1535-4989
- Publisher
- Amer Thoracic Soc
- Number of pages
- 13
- Grant note
- R01 HL092961; R21 HL132256; R01 HL142596; HL105355 / National Institutes of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA R21HL132256 / NATIONAL HEART, LUNG, AND BLOOD INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Heart Lung & Blood Institute (NHLBI)
- Language
- English
- Date published
- 11/01/2019
- Academic Unit
- Anatomy and Cell Biology
- Record Identifier
- 9984949238702771
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