Gallardo Felipe S, Córdova-Casanova Adriana, Brandan Enrique
Centro de Envejecimiento y Regeneración, CARE Chile UC, Santiago, Chile.
Departamento de Biología Celular y Molecular, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, Chile.
J Cell Commun Signal. 2021 Sep;15(3):317-334. doi: 10.1007/s12079-021-00610-w. Epub 2021 Mar 10.
Muscular dystrophies (MDs) are a diverse group of severe disorders characterized by increased skeletal muscle feebleness. In many cases, respiratory and cardiac muscles are also compromised. Skeletal muscle inflammation and fibrosis are hallmarks of several skeletal muscle diseases, including MDs. Until now, several keys signaling pathways and factors that regulate inflammation and fibrosis have been identified. However, no curative treatments are available. Therefore, it is necessary to find new therapeutic targets to fight these diseases and improve muscle performance. Lysophosphatidic acid (LPA) is an active glycerophospholipid mainly synthesized by the secreted enzyme autotaxin (ATX), which activates six different G protein-coupled receptors named LPA to LPA (LPARs). In conjunction, they are part of the ATX/LPA/LPARs axis, involved in the inflammatory and fibrotic response in several organs-tissues. This review recapitulates the most relevant aspects of inflammation and fibrosis in MDs. It analyzes experimental evidence of the effects of the ATX/LPA/LPARs axis on inflammatory and fibrotic responses. Finally, we speculate about its potential role as a new therapeutic pharmacological target to treat these diseases.
肌肉萎缩症（MDs）是一类严重的疾病，其特征是骨骼肌无力加剧。在许多情况下，呼吸肌和心肌也会受到影响。骨骼肌炎症和纤维化是包括肌肉萎缩症在内的几种骨骼肌疾病的标志。到目前为止，已经确定了几个调节炎症和纤维化的关键信号通路和因子。然而，目前尚无治愈性治疗方法。因此，有必要寻找新的治疗靶点来对抗这些疾病并改善肌肉功能。溶血磷脂酸（LPA）是一种活性甘油磷脂，主要由分泌酶自分泌运动因子（ATX）合成，它激活六种不同的G蛋白偶联受体，命名为LPA1至LPA6（LPARs）。它们共同构成了ATX/LPA/LPARs轴，参与多个器官组织的炎症和纤维化反应。本综述概述了肌肉萎缩症中炎症和纤维化的最相关方面。分析了ATX/LPA/LPARs轴对炎症和纤维化反应影响的实验证据。最后，我们推测其作为治疗这些疾病的新治疗药理学靶点的潜在作用。
