Bex1 knock out mice show altered skeletal muscle regeneration

Abstract

Bex1 and Calmodulin (CaM) are upregulated during skeletal muscle regeneration. We confirm this finding and demonstrate the novel finding that they interact in a calcium-dependent manner. To study the role of Bex1 and its interaction with CaM in skeletal muscle regeneration, we generated Bex1 knock out (Bex1-KO) mice. These mice appeared to develop normally and are fertile, but displayed a functional deficit in exercise performance compared to wild type (WT) mice. After intramuscular injection of cardiotoxin, which causes extensive and reproducible myotrauma followed by recovery, regenerating muscles of Bex1-KO mice exhibited elevated and prolonged cell proliferation, as well as delayed cell differentiation, compared to WT mice. Thus, our results provide the first evidence that Bex1-KO mice show altered muscle regeneration, and allow us to propose that the interaction of Bex1 with Ca2+/CaM may be involved in skeletal muscle regeneration.

The NAD+-Dependent SIRT1 Deacetylase Translates a Metabolic Switch into Regulatory Epigenetics in Skeletal Muscle Stem Cells

“…The H19 lncRNA, up-regulated in Cul (Figure 5D), was also increased in SIRT1 mKO SCs induced to differentiate (Figure S5C). Of particular interest, transcripts typically expressed in either embryonic muscle and/or upregulated during muscle regeneration including the embryonic myosin heavy chain isoform ( Myh3 ), filamin C ( Flnc ), and brain expressed 1 ( Bex1 ) were increased in SIRT1 mKO SCs (Goetsch et al, 2005; Koo et al, 2007; Weydert et al, 1987, Table S2, see below Figure 7G). …”

Macrophage PPARγ, a Lipid Activated Transcription Factor Controls the Growth Factor GDF3 and Skeletal Muscle Regeneration

“…The list of the differentially regulated genes (Fig 7E and Table S2) showed that a limited set of transcripts were either induced or repressed in the presence of GDF3. Several of the differentially regulated genes, including Bex1, (Jiang et al, 2016; Koo et al, 2007), Sgca (Matsumura et al, 1992) and Camk1g, have been implicated in muscle regeneration, muscle structure and/or Ca 2+ homeostasis, showing that macrophage derived GDF3 could elicit biologically relevant changes during muscle regeneration.…”

Single-Cell Resolution of Temporal Gene Expression during Heart Development

“…These transitional CM expressed genes involved in cellular growth (e.g., Tcea1 , encoding transcription elongation factor), CM differentiation ( Cbx3 an epigenetic silencer that promotes pluripotent cells differentiation; Casq2, calsequestrin 2; Ckm, creatinine kinase) and the metabolic switch from glycolysis (reduced Pgam1 expression) to fatty acid oxidation (increased Fabp3 , Fabp4 , encoding fatty acid binding protein; Fig 4C ) that characterizes mature CMs (Vander Heiden et al, 2010). Further maturation occurred by P21 when there was decreased expression of calmodulin-interacting proteins, Bex1 and Bex4, that promote muscle regeneration (Koo et al, 2007). …”