Resistin-like molecule-β (RELM-β) targets airways fibroblasts to effect remodelling in asthma: From mouse to man

C. L. Fang, L. J. Yin, S. Sharma, S. Kierstein, H. F. Wu, G. Eid, Angela Franciska Haczku, C. J. Corrigan, S. Ying

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

Background: RELM-β has been implicated in airways inflammation and remodelling in murine models. Its possible functions in human airways are largely unknown. The aim was to address the hypothesis that RELM-β plays a role in extracellular matrix deposition in asthmatic airways. Methods: The effects of RELM-β gene deficiency were studied in a model of allergen exposure in mice sensitised and challenged with Aspergillus fumigatus (Af). RELM-β expression was investigated in bronchial biopsies from asthmatic patients. Direct regulatory effects of RELM-β on human lung fibroblasts were examined using primary cultures and the MRC5 cell line in vitro. Results: Sensitisation and challenge of wild-type mice with Af-induced release of RELM-β with a time course coincident with that of procollagen in the airways. Af-induced expression of mRNA encoding some, but not all ECM in the lung parenchyma was attenuated in RELM-β-/- mice. RELM-β expression was significantly increased in the bronchial submucosa of human asthmatics compared with controls, and its expression correlated positively with that of fibronectin and α-smooth muscle actin. In addition to epithelial cells, macrophages, fibroblasts and vascular endothelial cells formed the majority of cells expressing RELM-β in the submucosa. Exposure to RELM-β increased TGF-β1, TGF-β2, collagen I, fibronectin, smooth muscle α-actin, laminin α1, and hyaluronan and proteoglycan link protein 1 (Hapl1) production as well as proliferation by human lung fibroblasts in vitro. These changes were associated with activation of ERK1/2 in MRC5 cells. Conclusion: The data are consistent with the hypothesis that elevated RELM-β expression in asthmatic airways contributes to airways remodelling at least partly by increasing fibroblast proliferation and differentiation with resulting deposition of extracellular matrix proteins.

Original languageEnglish (US)
Pages (from-to)940-952
Number of pages13
JournalClinical and Experimental Allergy
Volume45
Issue number5
DOIs
StatePublished - May 1 2015
Externally publishedYes

Keywords

  • Asthma
  • Collagen
  • Fibronectin
  • RELM-β
  • Remodelling
  • TGF-β

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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