Activation of the ATX/LPA/LPARs axis induces a fibrotic response in skeletal muscle

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dc.contributor.authorCordova-Casanova, Adriana
dc.contributor.authorCruz-Soca, Meilyn
dc.contributor.authorChun, Jerold
dc.contributor.authorCarlos Casar, Juan
dc.contributor.authorBrandan, Enrique
dc.date.accessioned2025-01-20T21:07:35Z
dc.date.available2025-01-20T21:07:35Z
dc.date.issued2022
dc.description.abstractSeveral common chronic diseases, muscular dystrophies (MDs), and aging lead to progressive fibrous connective tissue (fibrosis) accumulation in skeletal muscle. Cumulative past evidence points to the role of signaling lipids such as lysophosphatidic acid (LPA) and its receptors (LPARs) in different models of fibrosis. However, the potential contribution of these molecules to the fibrotic process in skeletal muscle has not been explored. Here, we show the expression of ATX/LPA/LPARs axis components in skeletal muscle, which suggests their potential relevance for the biology of this tissue. We investigated if the skeletal muscle responds to the stimulus of intramuscular (IM) LPA injections, finding an early induction of the pro-fibrotic factor connective tissue growth factor/Cellular Communication Network factor 2 (CCN2) and extracellular matrix (ECM) proteins. Also, we found that LPA induces an increase in the number of fibro/adipogenic progenitors (FAPs), which are the primary cellular source of myofibroblasts. These effects were for the most part prevented by the inhibitor Ki16425, which inhibits the LPA receptors LPA(1) and LPA(3), as well as in the LPA(1)-KO mice. We also evaluated the in vivo activation of extracellular signal-regulated kinases (ERK 1/2), AKT, c-Jun N-terminal kinase (JNK), and Yes-asocciated protein 1 (YAP) in response to LPA. Our results show that LPA induces ERK 1/2 phosphorylation in WT muscle, but not in LPA1-KO mice. Treatment with the ERK 1/2 inhibitor U0126 prevented the induction of fibronectin in response to LPA, suggesting that this pathway is involved in LPA-induced fibrosis. Altogether, these results demonstrate that ATX/LPA/LPARs constitute a pro-fibrotic axis and suggest a possible role in muscular diseases. (C) 2022 Elsevier B.V. All rights reserved.
dc.fuente.origenWOS
dc.identifier.doi10.1016/j.matbio.2022.03.008
dc.identifier.eissn1569-1802
dc.identifier.issn0945-053X
dc.identifier.urihttps://doi.org/10.1016/j.matbio.2022.03.008
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/93423
dc.identifier.wosidWOS:000795917200007
dc.language.isoen
dc.pagina.final139
dc.pagina.inicio121
dc.revistaMatrix biology
dc.rightsacceso restringido
dc.subjectFibrosis
dc.subjectLysophosphatidic acid
dc.subjectLPARs
dc.subjectAutotaxin
dc.subjectMuscular dystrophies
dc.subject.ods03 Good Health and Well-being
dc.subject.odspa03 Salud y bienestar
dc.titleActivation of the ATX/LPA/LPARs axis induces a fibrotic response in skeletal muscle
dc.typeartículo
dc.volumen109
sipa.indexWOS
sipa.trazabilidadWOS;2025-01-12
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