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Publication : Atx regulates skeletal muscle regeneration via LPAR1 and promotes hypertrophy.

First Author  Ray R Year  2021
Journal  Cell Rep Volume  34
Issue  9 Pages  108809
PubMed ID  33657371 Mgi Jnum  J:304277
Mgi Id  MGI:6694816 Doi  10.1016/j.celrep.2021.108809
Citation  Ray R, et al. (2021) Atx regulates skeletal muscle regeneration via LPAR1 and promotes hypertrophy. Cell Rep 34(9):108809
abstractText  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.
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