| First Author | Bonala S | Year | 2012 |
| Journal | J Biol Chem | Volume | 287 |
| Issue | 16 | Pages | 12935-51 |
| PubMed ID | 22362769 | Mgi Jnum | J:184373 |
| Mgi Id | MGI:5320818 | Doi | 10.1074/jbc.M111.319145 |
| Citation | Bonala S, et al. (2012) Peroxisome proliferator-activated receptor beta/delta induces myogenesis by modulating myostatin activity. J Biol Chem 287(16):12935-51 |
| abstractText | Classically, peroxisome proliferator-activated receptor beta/delta (PPARbeta/delta) function was thought to be restricted to enhancing adipocyte differentiation and development of adipose-like cells from other lineages. However, recent studies have revealed a critical role for PPARbeta/delta during skeletal muscle growth and regeneration. Although PPARbeta/delta has been implicated in regulating myogenesis, little is presently known about the role and, for that matter, the mechanism(s) of action of PPARbeta/delta in regulating postnatal myogenesis. Here we report for the first time, using a PPARbeta/delta-specific ligand (L165041) and the PPARbeta/delta-null mouse model, that PPARbeta/delta enhances postnatal myogenesis through increasing both myoblast proliferation and differentiation. In addition, we have identified Gasp-1 (growth and differentiation factor-associated serum protein-1) as a novel downstream target of PPARbeta/delta in skeletal muscle. In agreement, reduced Gasp-1 expression was detected in PPARbeta/delta-null mice muscle tissue. We further report that a functional PPAR-responsive element within the 1.5-kb proximal Gasp-1 promoter region is critical for PPARbeta/delta regulation of Gasp-1. Gasp-1 has been reported to bind to and inhibit the activity of myostatin; consistent with this, we found that enhanced secretion of Gasp-1, increased Gasp-1 myostatin interaction and significantly reduced myostatin activity upon L165041-mediated activation of PPARbeta/delta. Moreover, we analyzed the ability of hGASP-1 to regulate myogenesis independently of PPARbeta/delta activation. The results revealed that hGASP-1 protein treatment enhances myoblast proliferation and differentiation, whereas silencing of hGASP-1 results in defective myogenesis. Taken together these data revealed that PPARbeta/delta is a positive regulator of skeletal muscle myogenesis, which functions through negatively modulating myostatin activity via a mechanism involving Gasp-1. |
