Project description:Excessive or sustained glucocorticoid (GC) exposure causes muscle wasting. Paradoxically, moderate or transient GC exposure elicits ergogenic effects, evidenced by their widespread use as doping agents by endurance athletes and poorly understood efficacy in Duchenne muscular dystrophy (DMD), a genetic muscle wasting disease. While mechanisms underlying GC-mediated muscle wasting are well defined, the molecular basis for the latter remains unknown. In this arm of our studies, we compare expression profiles in quadriceps tissue from KLF15 transgenic (MTg) and non-Tg mice.
Project description:We previously demonstrated that the transcription factor, KLF15, is a glucocorticoid-regulated gene that represses primary human airway smooth muscle (ASM) proliferation. Here, we show that KLF15 also represses ASM hypertrophy. To uncover the mechanistic basis for these effects, we integrated transcriptome data from KLF15 over-expression with genome-wide analysis of RNA Polymerase II (RNAPII) and glucocorticoid receptor (GR) occupancy (i.e. ChIP-seq). This led us to identify PLCD1 as both a KLF15-regulated gene and a repressor of ASM hypertrophy.
Project description:Excessive or sustained glucocorticoid (GC) exposure causes muscle wasting. Paradoxically, moderate or transient GC exposure elicits ergogenic effects, evidenced by their widespread use as doping agents by endurance athletes and poorly understood efficacy in Duchenne muscular dystrophy (DMD), a genetic muscle wasting disease. While mechanisms underlying GC-mediated muscle wasting are well defined, the molecular basis for the latter remains unknown. In this arm of our studies, Wild-type (WT) and Klf15-/- (KO) mice were given the potent GC receptor agonist dexamethasone (dex) and quadriceps tissue was subjected to transcript expression profiling by cDNA microarrays.
Project description:Analysis of soleus (SOL) muscle isolated from wildtype (WT) and Mettl21cLacZ/LacZ mice (KO). Results provide unbiased gene expression profile of SOL muscle after Mettl21c deletion.
Project description:The effect of acetyl-L-carnitine (ALCAR) supplementation to hindlimb suspended rats has been analyzed in order to test whether this would promote the differentiation towards an oxidative phenotype of muscle fibers in soleus muscle and prevent the transformation of this slow tonic muscle towards a glycolytic, low-oxidative phenotype due to unloading condition. 3 month-old rats were daily supplemented with ALCAR concomitantly with hindlimb suspension. Validated microarray analysis for a broad range of muscle-relevant processes delineated an ALCAR-induced adjustment of the expression profile. In particular, transcript elevations of factors underlying oxidative metabolism in mitochondria and protein turnover by ribosomal and proteasomal components as well as an adaptation of voltage-gated ion channel expression were identified as an ALCAR response in soleus muscle. Keywords: ALCAR effect