Exaggerated BMP4 signalling alters human airway basal progenitor cell differentiation to cigarette smoking-related phenotypes

Wu Lin Zuo, Jing Yang, Yael Strulovici-Barel, Jacqueline Salit, Mahboubeh Rostami, Jason G. Mezey, Sarah L. O'Beirne, Robert J. Kaner, Ronald Crystal

Research output: Contribution to journalArticle

Abstract

Airway remodelling in chronic obstructive pulmonary disease (COPD) originates, in part, from smoking-induced changes in airway basal stem/progenitor cells (BCs). Based on the knowledge that bone morphogenetic protein 4 (BMP4) influences epithelial progenitor function in the developing and adult mouse lung, we hypothesised that BMP4 signalling may regulate the biology of adult human airway BCs relevant to COPD.BMP4 signalling components in human airway epithelium were analysed at the mRNA and protein levels, and the differentiation of BCs was assessed using the BC expansion and air-liquid interface models in the absence/presence of BMP4, BMP receptor inhibitor and/or small interfering RNAs against BMP receptors and downstream signalling.The data demonstrate that in cigarette smokers, BMP4 is upregulated in ciliated and intermediate undifferentiated cells, and expression of the BMP4 receptor BMPR1A is enriched in BCs. BMP4 induced BCs to acquire a smoking-related abnormal phenotype in vitro mediated by BMPR1A/Smad signalling, characterised by decreased capacity to differentiate into normal mucociliary epithelium, while generating squamous metaplasia.Exaggerated BMP4 signalling promotes cigarette smoking-relevant airway epithelial remodelling by inducing abnormal phenotypes in human airway BCs. Targeting of BMP4 signalling in airway BCs may represent a novel target to prevent/treat COPD-associated airway disease.

Original languageEnglish
JournalThe European respiratory journal
Volume53
Issue number5
DOIs
Publication statusPublished - 1 May 2019

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Bone Morphogenetic Protein 4
Stem Cells
Smoking
Phenotype
Bone Morphogenetic Protein Receptors
Chronic Obstructive Pulmonary Disease
Airway Remodeling
Epithelium

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

Cite this

Exaggerated BMP4 signalling alters human airway basal progenitor cell differentiation to cigarette smoking-related phenotypes. / Zuo, Wu Lin; Yang, Jing; Strulovici-Barel, Yael; Salit, Jacqueline; Rostami, Mahboubeh; Mezey, Jason G.; O'Beirne, Sarah L.; Kaner, Robert J.; Crystal, Ronald.

In: The European respiratory journal, Vol. 53, No. 5, 01.05.2019.

Research output: Contribution to journalArticle

Zuo, Wu Lin ; Yang, Jing ; Strulovici-Barel, Yael ; Salit, Jacqueline ; Rostami, Mahboubeh ; Mezey, Jason G. ; O'Beirne, Sarah L. ; Kaner, Robert J. ; Crystal, Ronald. / Exaggerated BMP4 signalling alters human airway basal progenitor cell differentiation to cigarette smoking-related phenotypes. In: The European respiratory journal. 2019 ; Vol. 53, No. 5.
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