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Periostin: contributor to abnormal airway epithelial function in asthma?

Janette K. Burgess, Marnix R. Jonker, Marijn Berg, Nick T.H. ten Hacken, Kerstin B. Meyer, Maarten van den Berge, Martijn C. Nawijn, Irene H. Heijink
European Respiratory Journal 2021 57: 2001286; DOI: 10.1183/13993003.01286-2020
Janette K. Burgess
1Dept of Pathology and Medical Biology, Experimental Pulmonology and Inflammation Research, University of Groningen, University Medical Centre Groningen, Groningen, The Netherlands
2GRIAC Research Institute, University of Groningen, University Medical Centre Groningen, Groningen, The Netherlands
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Marnix R. Jonker
1Dept of Pathology and Medical Biology, Experimental Pulmonology and Inflammation Research, University of Groningen, University Medical Centre Groningen, Groningen, The Netherlands
2GRIAC Research Institute, University of Groningen, University Medical Centre Groningen, Groningen, The Netherlands
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Marijn Berg
1Dept of Pathology and Medical Biology, Experimental Pulmonology and Inflammation Research, University of Groningen, University Medical Centre Groningen, Groningen, The Netherlands
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Nick T.H. ten Hacken
3Dept of Pulmonology, University of Groningen, University Medical Centre Groningen, Groningen, The Netherlands
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Kerstin B. Meyer
4Wellcome Sanger Institute, Wellcome Genome Campus, Cambridge, UK
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Maarten van den Berge
2GRIAC Research Institute, University of Groningen, University Medical Centre Groningen, Groningen, The Netherlands
3Dept of Pulmonology, University of Groningen, University Medical Centre Groningen, Groningen, The Netherlands
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Martijn C. Nawijn
1Dept of Pathology and Medical Biology, Experimental Pulmonology and Inflammation Research, University of Groningen, University Medical Centre Groningen, Groningen, The Netherlands
2GRIAC Research Institute, University of Groningen, University Medical Centre Groningen, Groningen, The Netherlands
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Irene H. Heijink
1Dept of Pathology and Medical Biology, Experimental Pulmonology and Inflammation Research, University of Groningen, University Medical Centre Groningen, Groningen, The Netherlands
2GRIAC Research Institute, University of Groningen, University Medical Centre Groningen, Groningen, The Netherlands
3Dept of Pulmonology, University of Groningen, University Medical Centre Groningen, Groningen, The Netherlands
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Abstract

Periostin (POSTN) may serve as a biomarker for Type-2 mediated eosinophilic airway inflammation in asthma. We hypothesised that a Type-2 cytokine, interleukin (IL)-13, induces airway epithelial expression of POSTN, which in turn contributes to epithelial changes observed in asthma.

We studied the effect of IL-13 on POSTN expression in BEAS-2B and air–liquid interface differentiated primary bronchial epithelial cells (PBECs). Additionally, the effects of recombinant human POSTN on epithelial-to-mesenchymal transition (EMT) markers and mucin genes were assessed. POSTN single cell gene expression and protein levels were analysed in bronchial biopsies and induced sputum from asthma patients and healthy controls.

IL-13 increased POSTN expression in both cell types and this was accompanied by EMT-related features in BEAS-2B. In air–liquid interface differentiated PBECs, IL-13 increased POSTN basolateral and apical release. Apical administration of POSTN increased the expression of MMP-9, MUC5B and MUC5AC. In bronchial biopsies, POSTN expression was mainly confined to basal epithelial cells, ionocytes, endothelial cells and fibroblasts, showing higher expression in basal epithelial cells from asthma patients versus those from controls. A higher level of POSTN protein expression in epithelial and subepithelial layers was confirmed in bronchial biopsies from asthma patients when compared to healthy controls. Although sputum POSTN levels were not higher in asthma, levels correlated with eosinophil numbers and with the coughing-up of mucus.

POSTN expression is increased by IL-13 in bronchial epithelial cells and is higher in bronchial biopsies from asthma patients. This may have important consequences, as administration of POSTN increases epithelial expression of mucin genes, supporting the relationship of POSTN with Type-2 mediated asthma and mucus secretion.

Abstract

High levels of IL-13 in Type-2 driven asthma play a crucial role in the development of the abnormal epithelial phenotype by induction of periostin (POSTN) secretion. POSTN induces mucin production in airway epithelial cells. https://bit.ly/3hg7ETu

Footnotes

  • This article has supplementary material available from erj.ersjournals.com

  • Conflict of interest: J.K. Burgess has nothing to disclose.

  • Conflict of interest: M.R. Jonker has nothing to disclose.

  • Conflict of interest: M. Berg has nothing to disclose.

  • Conflict of interest: N.T.H. ten Hacken has nothing to disclose.

  • Conflict of interest: K.B. Meyer has nothing to disclose.

  • Conflict of interest: M. van den Berge reports research grants paid to their institution from AstraZeneca, Novartis and Genentech, outside the submitted work.

  • Conflict of interest: M.C. Nawijn reports grants from Lung Foundation Netherlands (grant numbers 5.1.14.020 and 4.1.18.226), GSK Ltd, the European Commission (grant number 874656, discovAIR) and the Chan Zuckerberg Initiative, during the conduct of the study.

  • Conflict of interest: I.H. Heijink reports grants from Roche, during the conduct of the study; and grants from the Netherlands Lung Foundation and Boehringer Ingelheim, outside the submitted work.

  • Support statement: This study was supported by research grants from Roche (HLR-14) to I.H. Heijink and from the Netherlands Lung Foundation to M.C. Nawijn (LF5.1.14.020 and LF4.1.18.226). Funding information for this article has been deposited with the Crossref Funder Registry.

  • Received April 20, 2020.
  • Accepted August 17, 2020.
  • ©ERS 2021. For reproduction rights and permissions contact permissions{at}ersnet.org
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Periostin: contributor to abnormal airway epithelial function in asthma?
Janette K. Burgess, Marnix R. Jonker, Marijn Berg, Nick T.H. ten Hacken, Kerstin B. Meyer, Maarten van den Berge, Martijn C. Nawijn, Irene H. Heijink
European Respiratory Journal Feb 2021, 57 (2) 2001286; DOI: 10.1183/13993003.01286-2020

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Periostin: contributor to abnormal airway epithelial function in asthma?
Janette K. Burgess, Marnix R. Jonker, Marijn Berg, Nick T.H. ten Hacken, Kerstin B. Meyer, Maarten van den Berge, Martijn C. Nawijn, Irene H. Heijink
European Respiratory Journal Feb 2021, 57 (2) 2001286; DOI: 10.1183/13993003.01286-2020
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