The role of satellite cell derived TRIM28 in mechanical loading‐induced and injury‐induced myogenesis

Abstract

Using a global phosphoproteomics‐based approach, we discovered that mechanical loading leads to a very robust increase in the phosphorylation of the S473 residue on TRIM28. Immunohistochemical analysis also revealed that the increase in TRIM28(S473) phosphorylation predominantly occurs within the myonuclei and satellite cells. The alteration in satellite cells was particularly intriguing because satellite cells function as muscle stem cells that can become activated in response to stimuli such as mechanical loading and injury. Once activated, satellite cells can undergo myogenesis which leads to the myonuclear accretion or the generation of new myofibers. Of note, many studies have reported that satellite cells are necessary for the mechanical loading‐induced growth of pre‐existing myofibers, as well as the formation of new myofibers that occur in response to injury. Furthermore, it has been reported that phosphorylation of the S473 residue on TRIM28 can unleash the transcriptional activity of MyoD and Mef2 (two key transcription factors that drive satellite cell‐mediated myogenesis). Inspired by these points, we generated satellite cell specific and tamoxifen‐inducible TRIM28 knockout mice and then used these mice to discover that satellite cell derived TRIM28 is not only required for the normal myonuclear accretion that occurs in response to mechanical loading, but also the regeneration of myofibers following an injury. Furthermore, in vitro analyses revealed that the knockdown of TRIM28 leads to a fusion defect in primary myoblast. Taken together, these findings unravel a novel role of satellite cell‐derived TRIM28 in mechanical loading‐induced and injury induced myogenesis.