Regulation of lung autophagy by proteinase-activated receptor 2 activation

K Mccallum*, L Dunning, L Mcgarvey, M Hollywood, J Brzeszczynska, C Goodyear, J Lockhart, A Crilly, G Litherland

*Corresponding author for this work

Research output: Contribution to journalMeeting Abstractpeer-review

3 Downloads (Pure)

Abstract

Lungs from patients with chronic obstructive pulmonary disease (COPD) display hallmarks of premature ageing, including dysregulated autophagy, leading to cellular senescence. The underlying mechanisms remain unclear. Proteinase activated receptor 2 (PAR2) is a potential therapeutic target for inflammatory conditions, with documented roles in lung pathology. A role for this receptor in lung ageing is yet unexplored.

Autophagic markers LC3 and ATG7 were examined in C57BL/6 wild type and PAR2-/- knock out lung tissue using immunohistochemistry. Autophagic flux was quantified through Marfluorescent imaging (CYTO-ID detection kit) in human bronchial epithelial cell line BEAS-2B and primary human bronchial epithelial cells from healthy (HBEC) and COPD patient donors (DHBEC), after PAR2 stimulation with SLIGKV agonist (cf. VKGILS control).

ATG7 (plt;0.005) and LC3 (plt;0.05) positive cells were significantly upregulated in PAR2-deficient lungs (Figure 1). PAR2 was present on epithelial cultures, with redistribution upon stimulation. PAR2 stimulation in BEAS-2B resulted in a significant reduction of autophagic vesicles cf. VKGILS (plt;0.001). Whilst similar behaviour was observed in HBEC, DHBEC exhibited autophagic flux dysregulation.

This study provides the first data describing a role for PAR2 in the regulation of autophagy in airway epithelia, suggesting a potential mechanism that may underpin premature lung ageing in conditions such as COPD.
Original languageEnglish
Article number75
JournalERJ Open Research
Volume6
Issue numbersuppl 5
DOIs
Publication statusPublished - 15 Apr 2020

Keywords

  • COPD - mechanism
  • inflammation
  • COPD

Fingerprint Dive into the research topics of 'Regulation of lung autophagy by proteinase-activated receptor 2 activation'. Together they form a unique fingerprint.

Cite this