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LSC - 2021 - Investigating the role of vitamin A intake and retinoic acid signalling in lung homeostasis and repair-A multidisciplinary approach

Mongey Róisín, Sally Yunsun Kim, Diana Van Der Plaat, Cosetta Minelli, Charlotte Dean, Matthew Hind
European Respiratory Journal 2021 58: PA3624; DOI: 10.1183/13993003.congress-2021.PA3624
Mongey Róisín
1Imperial College London, London, United Kingdom
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  • For correspondence: r.mongey16@imperial.ac.uk
Sally Yunsun Kim
1Imperial College London, London, United Kingdom
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Diana Van Der Plaat
1Imperial College London, London, United Kingdom
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Cosetta Minelli
1Imperial College London, London, United Kingdom
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Charlotte Dean
1Imperial College London, London, United Kingdom
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Matthew Hind
1Imperial College London, London, United Kingdom
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Abstract

Retinoic acid (RA), obtained wholly from dietary sources, is essential for lung development and can induce alveolar regeneration in a number of animal models of alveolar insufficiency. The mechanisms by which RA mediates lung repair however remain unclear. To assess the role of vitamin (vit) A and RA signalling in the lung we used a multi-disciplinary, epidemiological and lab-based approach. Linear regression analysis of the UK Biobank population (n=500,000) to assess the effect of dietary vit A on adult lung function identified a positive association between increased vit A intake and Forced vital capacity (FVC) and a protective effect on FVC in smokers. In addition, analysis of RA pathway genes identified multiple SNPs which significantly modulate FVC. To determine the cell and molecular mechanisms of how RA might modulate lung repair, we developed a novel model using precision cut lung slices (PCLS) and HCl to generate a restricted area of damage to study cellular responses in both injured and uninjured regions of lung tissue. Following injury, inhibition of RA signalling with Diethylaminobenzaldehyde, an inhibitor of RA synthesis and BMS493, a pan-RAR inverse agonist, reduced proliferation in PCLS. Interestingly exposure to increased exogenous RA also abrogated proliferation in addition to increasing progenitor cell number. We believe this may be an indication that RA promotes proliferation within a narrow concentration window which is then prevented when levels of RA production and signalling are decreased with inhibitors or increased with exogenous RA. These data support a role for vit A and RA in lung homeostasis and provide further insight into mechanisms that contribute to regeneration of the lung.

Footnotes

Cite this article as: European Respiratory Journal 2021; 58: Suppl. 65, PA3624.

This abstract was presented at the 2021 ERS International Congress, in session “Prediction of exacerbations in patients with COPD”.

This is an ERS International Congress abstract. No full-text version is available. Further material to accompany this abstract may be available at www.ers-education.org (ERS member access only).

  • Copyright ©the authors 2021
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LSC - 2021 - Investigating the role of vitamin A intake and retinoic acid signalling in lung homeostasis and repair-A multidisciplinary approach
Mongey Róisín, Sally Yunsun Kim, Diana Van Der Plaat, Cosetta Minelli, Charlotte Dean, Matthew Hind
European Respiratory Journal Sep 2021, 58 (suppl 65) PA3624; DOI: 10.1183/13993003.congress-2021.PA3624

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LSC - 2021 - Investigating the role of vitamin A intake and retinoic acid signalling in lung homeostasis and repair-A multidisciplinary approach
Mongey Róisín, Sally Yunsun Kim, Diana Van Der Plaat, Cosetta Minelli, Charlotte Dean, Matthew Hind
European Respiratory Journal Sep 2021, 58 (suppl 65) PA3624; DOI: 10.1183/13993003.congress-2021.PA3624
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