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Title: [Retracted] Peroxisome proliferator-activated receptor β/δ induces myogenesis by modulating myostatin activity
Authors: Bonala, Sabeera
Lokireddy, Sudarsanareddy
Arigela, Harikumar
Teng, Serena
Wahli, Walter
Sharma, Mridula
McFarlane, Craig
Kambadur, Ravi
Keywords: DRNTU::Science::Biological sciences::Biochemistry
Issue Date: 2012
Source: Bonala, S., Lokireddy, S., Arigela, H., Teng, S., Wahli, W., Sharma, M., et al. (2012). Peroxisome proliferator-activated receptor β/δ induces myogenesis by modulating myostatin activity. Journal of biological chemistry, 287(16), 12935-12951. [Retracted]
Series/Report no.: Journal of biological chemistry
Abstract: Classically, peroxisome proliferator-activated receptor β/δ (PPARβ/δ) 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 PPARβ/δ during skeletal muscle growth and regeneration. Although PPARβ/δ has been implicated in regulating myogenesis, little is presently known about the role and, for that matter, the mechanism(s) of action of PPARβ/δ in regulating postnatal myogenesis. Here we report for the first time, using a PPARβ/δ-specific ligand (L165041) and the PPARβ/δ-null mouse model, that PPARβ/δ 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 PPARβ/δ in skeletal muscle. In agreement, reduced Gasp-1 expression was detected in PPARβ/δ-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 PPARβ/δ 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 PPARβ/δ. Moreover, we analyzed the ability of hGASP-1 to regulate myogenesis independently of PPARβ/δ 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 PPARβ/δ is a positive regulator of skeletal muscle myogenesis, which functions through negatively modulating myostatin activity via a mechanism involving Gasp-1.
DOI: 10.1074/jbc.M111.319145
Rights: © 2012 by The American Society for Biochemistry and Molecular Biology, Inc
Fulltext Permission: none
Fulltext Availability: No Fulltext
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