Aberrant nonfibrotic parenchyma in idiopathic pulmonary fibrosis is correlated with decreased β-catenin inhibition and increased Wnt5a/b interaction

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Abstract

Idiopathic pulmonary fibrosis (IPF), an insidious disease with grave prognosis, is characterized by heterogeneous fibrosis with densely fibrotic areas surrounded by nonfibrotic normal-looking tissue, believed to reflect a temporal development. The etiology is incompletely elucidated, but aberrant wound healing is believed to be involved. Embryonic signaling pathways, including Wnt signaling, are reactivated in wound healing, and we therefore aimed to investigate Wnt signaling, and hypothesized that Wnt signaling would correspond to degree of fibrosis. Material from 10 patients with IPF were included (four diagnostic biopsies and six donated lungs) and compared to healthy controls (n = 7). We investigated markers of Wnt signaling (β-catenin, Wnt3a, ICAT, Wnt5a/b, DAAM1 and NLK) histologically in lung parenchyma with variable degree of fibrosis. Our results suggest that Wnt signaling is significantly altered (P < 0.05) already in normal-looking parenchyma. The expression of Wnt3a and ICAT decreased (both P < 0.01) in IPF compared to healthy lungs, whereas β-catenin, Wnt5a/b, DAAM1 and NLK increased (P < 0.05 for all). ICAT is further decreased in dense fibrosis compared to normal-looking parenchyma in IPF (P < 0.001). On the basis of our results, we conclude that from a Wnt perspective, there is no normal parenchyma in IPF, and Wnt signaling corresponds to degree of fibrosis. In addition, β-catenin and Wnt5a appears coupled, and decreased inhibition of β-catenin may be involved. We suggest that the interaction between β-catenin, ICAT, and Wnt5a/b may represent an important research area and potential target for therapeutic intervention.

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Authors
Organisations
External organisations
  • AstraZeneca, Sweden
  • Skåne University Hospital
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Physiology
Original languageEnglish
Article numbere12727
JournalPhysiological Reports
Volume4
Issue number5
Publication statusPublished - 2016
Publication categoryResearch
Peer-reviewedYes