The linkage between inflammation and fibrosis in muscular dystrophies: The axis autotaxin–lysophosphatidic acid as a new therapeutic target?

摘要

Model for the role of ATX/LPA/LPARs axis in MDs. ATX synthesizes LPA from lysophosphatidylcholine (LPC). LPA activates G-protein-coupled receptors (LPA1–6), triggering various cellular signaling in different cell types. LPA increases the expression of pro-fibrotic factors such as CCN2, and ECM proteins such as fibronectin, type I and III collagen in FAPs and myofibroblast. In neutrophils and MPs, LPA signaling increases inflammatory cytokines such as IL-1β, IL-4, IL-6, TNF-α, and some chemokines. This condition may lead to the activation of inflammation and fibrotic responses, impairing muscle performance. Created with biorender.com