Atx regulates skeletal muscle regeneration via LPAR1 and promotes hypertrophy

Document Type

Article

Publication Title

Cell Reports

Abstract

Muscle differentiation is a multifaceted and tightly controlled process required for the formation of skeletal muscle fibers. Satellite cells are the direct cellular contributors to muscle repair in injuries or disorders. Here, we show that autotaxin (Atx) expression and activity is required for satellite cell differentiation. Conditional ablation of Atx or its pharmacological inhibition impairs muscle repair. Mechanistically, we identify LPAR1 as the key receptor in Atx-LPA signaling. Myogenic gene array and pathway analysis identified that Atx-LPA signaling activates ribosomal protein S6 kinase (S6K), an mTOR-dependent master regulator of muscle cell growth via LPAR1. Furthermore, Atx transgenic mice show muscle hypertrophic effects and accelerated regeneration. Intramuscular injections of Atx/LPA show muscle hypertrophy. In addition, the regulatory effects of Atx on differentiation are conserved in human myoblasts. This study identifies Atx as a critical master regulator in murine and human muscles, identifying a promising extracellular ligand in muscle formation, regeneration, and hypertrophy. Satellite cells are indispensable for skeletal muscle formation or repair post-injury. Ray et al. identify that autotaxin (Atx) regulates the function of satellite cells through LPA-LPAR1 signaling. Muscle-specific loss of either Atx or LPAR1 impairs regeneration. In addition, Atx or LPA promotes hypertrophy.

DOI

10.1016/j.celrep.2021.108809

Publication Date

3-2-2021

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