Pharmacologic targeting of the ATX/LPA axis attenuates bleomycin-induced pulmonary fibrosis.
Pulm Pharmacol Ther
; 52: 32-40, 2018 10.
Article
en En
| MEDLINE
| ID: mdl-30201409
ABSTRACT
Idiopathic pulmonary fibrosis (IPF) is a chronic fibrosing lung disease with a dismal prognosis and a largely unknown etiology. Autotaxin (ATX) is a secreted lysophospholipase D, largely responsible for extracellular production of lysophosphatidic acid (LPA), a bioactive phospholipid. LPA has numerous effects in most cell types, signaling through at least 6 receptors (LPAR) exhibiting wide spread distribution and overlapping specificities. The ATX/LPA axis has been suggested as a therapeutic target in different chronic inflammatory and fibroproliferative disorders, including pulmonary fibrosis. In this report, we examined head-to-head the efficacy of a potent inhibitor of ATX (PF-8380), that has not been tested in pulmonary fibrosis models, and an antagonist of LPAR1 (AM095) in bleomycin (BLM)-induced pulmonary fibrosis. Both compounds abrogated the development of pulmonary fibrosis and prevented the distortion of lung architecture, exhibiting qualitative and quantitative differences in different manifestations of the modeled disease.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Piperazinas
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Benzoxazoles
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Compuestos de Bifenilo
/
Lisofosfolípidos
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Hidrolasas Diéster Fosfóricas
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Fibrosis Pulmonar Idiopática
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Isoxazoles
Tipo de estudio:
Qualitative_research
Límite:
Animals
Idioma:
En
Año:
2018
Tipo del documento:
Article