TY  - JOUR
PB  - EUROPEAN RESPIRATORY SOC JOURNALS LTD
N2  - 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.
Y1  - 2024/04/30/
UR  - https://doi.org/10.1183/16000617.0015-2024
N1  - 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
JF  - European Respiratory Review
TI  - Lysophosphatidic acid receptor 1 inhibition: a potential treatment target for pulmonary fibrosis
AV  - public
ID  - discovery10195035
VL  - 33
IS  - 172
SN  - 0905-9180
EP  - 18
A1  - Volkmann, Elizabeth R
A1  - Denton, Christopher P
A1  - Kolb, Martin
A1  - Wijsenbeek-Lourens, Marlies S
A1  - Emson, Claire
A1  - Hudson, Krischan
A1  - Amatucci, Anthony J
A1  - Distler, Oliver
A1  - Allanore, Yannick
A1  - Khanna, Dinesh
ER  -