Fig. 3.

Proposed functions for the ATX/LPA/LPARs axis in acute and chronic damage. Normal skeletal muscle regeneration is affected by the nature of the damage. Acute injuries are resolved by a well-orchestrated and transient increase of inflammatory cells and ECM-producing cells. The crosstalk between each cell population establishes a scaffolding network for proper muscle regeneration. On the other hand, as occurs in DMD patients, chronic insults result in persistent accumulation of both cell populations with enhanced capacities. We propose that the expression of ATX, and as a consequence an increase in LPA-mediated signaling, could be necessary for muscle regeneration by regulating SCs differentiation. Whether this axis is essential for acute ECM deposition and inflammation in skeletal muscle is unknown. Activation of LPA-mediated signaling induces some pathophysiological responses present in different organs and tissues in DMD. Some of them correspond to the induction of cytokines, chemokines, and fibrotic factors expression and the accumulation of myofibroblast, MPs, and neutrophils. If these effects are present in the skeletal muscle, this axis would be an attractive signaling pathway in future therapeutic considerations for MDs. Created with biorender.com