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- Title
Increased LGR6 Expression Sustains Long-Term Wnt Activation and Acquisition of Senescence in Epithelial Progenitors in Chronic Lung Diseases.
- Authors
Cortesi, Emanuela E.; Meeusen, Bob; Vanstapel, Arno; Verleden, Stijn E.; Vanaudenaerde, Bart M.; Wuyts, Wim A.; Janssens, Wim; Janssens, Veerle; Roskams, Tania; Ventura, Juan-José
- Abstract
Chronic lung diseases (CLDs) represent a set of disorders characterized by the progressive loss of proper lung function. Among severe CLDs, the incidence of chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF) has grown over the last decades, mainly in the elderly population. Several studies have highlighted an increased expression of senescence-related markers in the resident progenitor cells in COPD and IPF, possibly undermining epithelial integrity and contributing to the progression and the aggravation of both diseases. Recently, the chronic activation of the canonical Wnt/β-catenin pathway was shown to induce cellular senescence. Here, we investigated the localization and the expression of leucin-rich repeat-containing G-protein-coupled receptor 6 (LGR6), a protein that activates and potentiates the canonical Wnt signalling. Through immunohistochemical analyses, we identified a lesion-associated rise in LGR6 levels in abnormal lung epithelial progenitors in COPD and IPF when compared to histologically normal tissues. Moreover, in areas of aberrant regeneration, chronic damage and fibrosis, LGR6-expressing epithelial progenitors displayed a major increase in the expression of senescence-associated markers. Our study suggests the involvement of LGR6 in the chronic activation of the Wnt/β-catenin pathway, mediating the impairment and exhaustion of epithelial progenitors in COPD and IPF.
- Subjects
LUNG diseases; WNT signal transduction; LUNGS; IDIOPATHIC pulmonary fibrosis; CHRONIC obstructive pulmonary disease; CELLULAR aging; CHRONIC diseases
- Publication
Cells (2073-4409), 2021, Vol 10, Issue 12, p3437
- ISSN
2073-4409
- Publication type
Article
- DOI
10.3390/cells10123437