Proteinase activated receptor 2 modulates expression of autophagy markers in murine lungs

K. McCallum, L. Dunning, L. McGarvey, M. Hollywood, C.S. Goodyear, J. Brzeszczynska, A. Crilly, J.C. Lockhart, G.J. Litherland

Research output: Contribution to journalMeeting Abstract

Abstract

Chronic obstructive pulmonary disease (COPD) lungs display hallmarks of premature ageing, such as genomic instability, mitochondrial dysfunction, stem cell exhaustion, and dysregulation of autophagic mechanisms, ultimately contributing to epithelial cell death and induction of senescence (1). However, the underlying mechanisms remain unclear. While proteinase activated receptor 2 (PAR2) is a drug target for inflammatory conditions (2), with documented roles in lung pathology (fibrosis, airway remodelling and hyperactivity), a role for this receptor in lung ageing remains unexplored. Expression of autophagic markers LC3 and ATG7 were examined in C57BL/6 wild type and PAR2-/- knock out murine lung tissue using DAB immunohistochemistry, and % of positively stained cells within standardised regions of interest determined. ATG7 (mean ± SEM; WT 16.4 ± 5.8 % vs. PAR2-/- 77.4 ± 8.4%, n=3; p <0.005) and LC3 (mean ± SEM; WT 17.9± 7.9 % vs. PAR2-/- 46.2 ± 7.5%, n=6; p<0.05) were significantly upregulated in PAR2-deficient lung. LC3 expression was observed localised to distal airways, with ATG7 also located within the alveolar tissue. The data suggest a potential regulatory role for PAR2 in lung autophagy; modulation of receptor activity may therefore represent a novel potential therapeutic mechanism to alleviate the premature lung ageing seen in COPD. 1. Meiners S, Eickelberg O, Königshoff M. Hallmarks of the ageing lung. Eur Respir J 2015;45(3):807–27. 2. Heuberger DM, Schuepbach RA. Protease-activated receptors (PARs): Mechanisms of action and potential therapeutic modulators in PARdriven inflammatory diseases. Thromb J. 2019;17(1):1–24. This study was funded by the EU under the Interreg VA Programme, managed by the Special EU programmes body (SEUPB)
Original languageEnglish
Article number2.6
Pages (from-to)S270-S270
Number of pages1
JournalIrish Journal of Medical Science
Volume188
Issue numberSUPPL 10
DOIs
Publication statusPublished - 22 Nov 2019
EventIrish Thoracic Society Annual Scientific Meeting - The Galmont Hotel, Galway, Ireland
Duration: 21 Nov 201923 Nov 2019

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