Volkmann, Elizabeth R;
Denton, Christopher P;
Kolb, Martin;
Wijsenbeek-Lourens, Marlies S;
Emson, Claire;
Hudson, Krischan;
Amatucci, Anthony J;
... Khanna, Dinesh; + view all
(2024)
Lysophosphatidic acid receptor 1 inhibition: a potential treatment target for pulmonary fibrosis.
European Respiratory Review
, 33
(172)
, Article 240015. 10.1183/16000617.0015-2024.
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Abstract
Lysophosphatidic acid (LPA)-mediated activation of LPA receptor 1 (LPAR1) contributes to the pathophysiology of fibrotic diseases such as idiopathic pulmonary fibrosis (IPF) and systemic sclerosis (SSc). These diseases are associated with high morbidity and mortality despite current treatment options. The LPA-producing enzyme autotaxin (ATX) and LPAR1 activation contribute to inflammation and mechanisms underlying fibrosis in preclinical fibrotic models. Additionally, elevated levels of LPA have been detected in bronchoalveolar lavage fluid from patients with IPF and in serum from patients with SSc. Thus, ATX and LPAR1 have gained considerable interest as pharmaceutical targets to combat fibrotic disease and inhibitors of these targets have been investigated in clinical trials for IPF and SSc. The goals of this review are to summarise the current literature on ATX and LPAR1 signalling in pulmonary fibrosis and to help differentiate the novel inhibitors in development. The mechanisms of action of ATX and LPAR1 inhibitors are described and preclinical studies and clinical trials of these agents are outlined. Because of their contribution to numerous physiologic events underlying fibrotic disease, ATX and LPAR1 inhibition presents a promising therapeutic strategy for IPF, SSc and other fibrotic diseases that may fulfil unmet needs of the current standard of care.
| Type: | Article |
|---|---|
| Title: | Lysophosphatidic acid receptor 1 inhibition: a potential treatment target for pulmonary fibrosis |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1183/16000617.0015-2024 |
| Publisher version: | https://doi.org/10.1183/16000617.0015-2024 |
| Language: | English |
| Additional information: | Copyright © The authors 2024. This version is distributed under the terms of the Creative Commons Attribution Non-Commercial Licence 4.0. For commercial reproduction rights and permissions contact permissions@ersnet.org |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Inflammation |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10195035 |
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