Inactivation of PPARβ/δ adversely affects satellite cells and reduces postnatal myogenesis.

Détails

ID Serval
serval:BIB_D5029F0073D8
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Inactivation of PPARβ/δ adversely affects satellite cells and reduces postnatal myogenesis.
Périodique
American Journal of Physiology. Endocrinology and Metabolism
Auteur(s)
Chandrashekar P., Manickam R., Ge X., Bonala S., McFarlane C., Sharma M., Wahli W., Kambadur R.
ISSN
1522-1555 (Electronic)
ISSN-L
0193-1849
Statut éditorial
Publié
Date de publication
2015
Volume
309
Numéro
2
Pages
E122-E131
Langue
anglais
Résumé
Peroxisome proliferator-activated receptor β/δ (PPARβ/δ) is a ubiquitously expressed gene with higher levels observed in skeletal muscle. Recently, our laboratory showed (Bonala S, Lokireddy S, Arigela H, Teng S, Wahli W, Sharma M, McFarlane C, Kambadur R. J Biol Chem 287: 12935-12951, 2012) that PPARβ/δ modulates myostatin activity to induce myogenesis in skeletal muscle. In the present study, we show that PPARβ/δ-null mice display reduced body weight, skeletal muscle weight, and myofiber atrophy during postnatal development. In addition, a significant reduction in satellite cell number was observed in PPARβ/δ-null mice, suggesting a role for PPARβ/δ in muscle regeneration. To investigate this, tibialis anterior muscles were injured with notexin, and muscle regeneration was monitored on days 3, 5, 7, and 28 postinjury. Immunohistochemical analysis revealed an increased inflammatory response and reduced myoblast proliferation in regenerating muscle from PPARβ/δ-null mice. Histological analysis confirmed that the regenerated muscle fibers of PPARβ/δ-null mice maintained an atrophy phenotype with reduced numbers of centrally placed nuclei. Even though satellite cell numbers were reduced before injury, satellite cell self-renewal was found to be unaffected in PPARβ/δ-null mice after regeneration. Previously, our laboratory had showed (Bonala S, Lokireddy S, Arigela H, Teng S, Wahli W, Sharma M, McFarlane C, Kambadur R. J Biol Chem 287: 12935-12951, 2012) that inactivation of PPARβ/δ increases myostatin signaling and inhibits myogenesis. Our results here indeed confirm that inactivation of myostatin signaling rescues the atrophy phenotype and improves muscle fiber cross-sectional area in both uninjured and regenerated tibialis anterior muscle from PPARβ/δ-null mice. Taken together, these data suggest that absence of PPARβ/δ leads to loss of satellite cells, impaired skeletal muscle regeneration, and postnatal myogenesis. Furthermore, our results also demonstrate that functional antagonism of myostatin has utility in rescuing these effects.
Pubmed
Web of science
Création de la notice
29/06/2015 10:12
Dernière modification de la notice
20/08/2019 15:54
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