Open AccessAberrant nonfibrotic parenchyma in idiopathic pulmonary fibrosis is correlated with decreased β ‐catenin inhibition and increased Wnt5a/b interaction
Author(s) -
RydellTörmänen Kristina,
Zhou XiaoHong,
Hallgren Oskar,
Einarsson Jonas,
Eriksson Leif,
AnderssonSjöland Annika,
WestergrenThorsson Gunilla
Publication year - 2016
Publication title -
physiological reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.918
H-Index - 39
ISSN - 2051-817X
DOI - 10.14814/phy2.12727
Subject(s) - wnt signaling pathway , wnt3a , parenchyma , medicine , idiopathic pulmonary fibrosis , fibrosis , catenin , cancer research , pathology , pulmonary fibrosis , wnt5a , beta catenin , signal transduction , lung , biology , microbiology and biotechnology
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, DAAM 1 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, DAAM 1 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.