PMID:22040534

Citation	Angione, AR, Jiang, C, Pan, D, Wang, YX and Kuang, S (2011) PPARδ regulates satellite cell proliferation and skeletal muscle regeneration. Skelet Muscle 1:33
Abstract	ABSTRACT: Peroxisome proliferator-activated receptors (PPARs) are a class of nuclear receptors that play important roles in development and energy metabolism. Whereas PPARδ has been shown to regulate mitochondrial biosynthesis and slow-muscle fiber types, its function in skeletal muscle progenitors (satellite cells) is unknown. Since constitutive mutation of Pparδ leads to embryonic lethality, we sought to address this question by conditional knockout (cKO) of Pparδ using Myf5-Cre/Pparδflox/flox alleles to ablate PPARδ in myogenic progenitor cells. Although Pparδ-cKO mice were born normally and initially displayed no difference in body weight, muscle size or muscle composition, they later developed metabolic syndrome, which manifested as increased body weight and reduced response to glucose challenge at age nine months. Pparδ-cKO mice had 40% fewer satellite cells than their wild-type littermates, and these satellite cells exhibited reduced growth kinetics and proliferation in vitro. Furthermore, regeneration of Pparδ-cKO muscles was impaired after cardiotoxin-induced injury. Gene expression analysis showed reduced expression of the Forkhead box class O transcription factor 1 (FoxO1) gene in Pparδ-cKO muscles under both quiescent and regenerating conditions, suggesting that PPARδ acts through FoxO1 in regulating muscle progenitor cells. These results support a function of PPARδ in regulating skeletal muscle metabolism and insulin sensitivity, and they establish a novel role of PPARδ in muscle progenitor cells and postnatal muscle regeneration.
Links	PubMed PMC3223495 Online version:10.1186/2044-5040-1-33
Keywords
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
MOUSE:PPARD	involved_in	GO:0043415: positive regulation of skeletal muscle tissue regeneration	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete
MOUSE:PPARD	involved_in	GO:0045662: negative regulation of myoblast differentiation	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete
MOUSE:PPARD	involved_in	GO:0014842: regulation of skeletal muscle satellite cell proliferation	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete
MOUSE:PPARD		GO:0010628: positive regulation of gene expression	ECO:0000315:		P		Fig. 1EF	complete CACAO 2772
MOUSE:PPARD		GO:0014842: regulation of satellite cell proliferation	ECO:0000315:		P		Fig. 2ACD; positive regulation	complete CACAO 2773
MOUSE:PPARD		GO:0045662: negative regulation of myoblast differentiation	ECO:0000315:		P		Fig. 2E	complete CACAO 2774
MOUSE:PPARD		GO:0043415: positive regulation of skeletal muscle tissue regeneration	ECO:0000315:		P		Fig. 4(A-D)	complete CACAO 2775
MOUSE:PPARD		GO:2000288: positive regulation of myoblast proliferation	ECO:0000315:		P		Figure 3D, Ppard cKO muscle showed reduced growth rate of myoblasts cells compared to wild type.	complete CACAO 3208
MOUSE:PPARD	involved_in	GO:0010628: positive regulation of gene expression	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete
MOUSE:PPARD	involved_in	GO:2000288: positive regulation of myoblast proliferation	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete

References

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