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Article

Increased LGR6 Expression Sustains Long-Term Wnt Activation and Acquisition of Senescence in Epithelial Progenitors in Chronic Lung Diseases

1
Translational Cell & Tissue Research, Department of Imaging & Pathology, KU Leuven, 3000 Leuven, Belgium
2
Laboratory of Protein Phosphorylation and Proteomics, Department of Cellular and Molecular Medicine, KU Leuven, 3000 Leuven, Belgium
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Laboratory of Respiratory Diseases and Thoracic Surgery (BREATHE), Department of Chronic Diseases and Metabolism, KU Leuven, 3000 Leuven, Belgium
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Department of Pathology, UZ Leuven, 3000 Leuven, Belgium
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Department of Thoracic and Vascular Surgery & Pneumology, University Hospital Antwerp, 2650 Edegem, Belgium
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Antwerp Surgical Training, Anatomy and Research Centre (ASTARC), University of Antwerp, 2610 Wilrijk, Belgium
*
Authors to whom correspondence should be addressed.
Academic Editor: Konstantin G. Birukov
Cells 2021, 10(12), 3437; https://doi.org/10.3390/cells10123437
Received: 25 October 2021 / Revised: 28 November 2021 / Accepted: 3 December 2021 / Published: 7 December 2021
(This article belongs to the Special Issue Mucosal Immunity in Respiratory Diseases)
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. View Full-Text
Keywords: LGR6; COPD; IPF; senescence; lung; progenitor cells LGR6; COPD; IPF; senescence; lung; progenitor cells
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MDPI and ACS Style

Cortesi, E.E.; Meeusen, B.; Vanstapel, A.; Verleden, S.E.; Vanaudenaerde, B.M.; Wuyts, W.A.; Janssens, W.; Janssens, V.; Roskams, T.; Ventura, J.-J. Increased LGR6 Expression Sustains Long-Term Wnt Activation and Acquisition of Senescence in Epithelial Progenitors in Chronic Lung Diseases. Cells 2021, 10, 3437. https://doi.org/10.3390/cells10123437

AMA Style

Cortesi EE, Meeusen B, Vanstapel A, Verleden SE, Vanaudenaerde BM, Wuyts WA, Janssens W, Janssens V, Roskams T, Ventura J-J. Increased LGR6 Expression Sustains Long-Term Wnt Activation and Acquisition of Senescence in Epithelial Progenitors in Chronic Lung Diseases. Cells. 2021; 10(12):3437. https://doi.org/10.3390/cells10123437

Chicago/Turabian Style

Cortesi, Emanuela E., Bob Meeusen, Arno Vanstapel, Stijn E. Verleden, Bart M. Vanaudenaerde, Wim A. Wuyts, Wim Janssens, Veerle Janssens, Tania Roskams, and Juan-José Ventura. 2021. "Increased LGR6 Expression Sustains Long-Term Wnt Activation and Acquisition of Senescence in Epithelial Progenitors in Chronic Lung Diseases" Cells 10, no. 12: 3437. https://doi.org/10.3390/cells10123437

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