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LncRNA data in gastrocnemius muscles from mice that have undergone denervation of the right sciatic nerve or not

ABSTRACT: This study was to identify lncRNAs responsible for muscle atrophy Muscle atrophy commonly occurs in aging, disuse, starvation, and many chronic diseases including heart failure and cancer. Muscle atrophy leads to muscular weakness and reduced quality of life, which also significantly increases morbidity and mortality. While progress has been made in understanding the molecular underpinnings of muscle atrophy, currently there are no effective approved drugs to combat muscle atrophy. Thus, novel therapies for muscle atrophy would address an important unmet clinical need. Long non-coding RNAs (LncRNAs) are transcribed RNAs longer than 200 nucleotides with little or no protein-coding capacity. Several lncRNAs have been reported in myogenesis and few lncRNAs have been mechanistically linked to skeletal muscle diseases. Here we want to identify a lncRNA as a common regulator of multitypes of muscle atrophy.

ORGANISM(S): Mus musculus

PROVIDER: GSE151300 | GEO | 2021/01/06

REPOSITORIES: GEO

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Project description:Skeletal muscle atrophy is a debilitating condition associated with weakness, fatigue, and reduced functional capacity. Nuclear factor-kappaB (NF-κB) transcription factors play a critical role in atrophy. Knockout of genes encoding p50 or the NF-κB co-transactivator, Bcl-3, abolish disuse atrophy and thus they are NF-κB factors required for disuse atrophy. We do not know however, the genes targeted by NF-κB that produce the atrophied phenotype. Here we identify the genes required to produce disuse atrophy using gene expression profiling in wild type compared to Nfkb1 (gene encodes p50) and Bcl-3 deficient mice. There were 185 and 240 genes upregulated in wild type mice due to unloading, that were not upregulated in Nfkb1-/- and Bcl-3-/- mice, respectively, and so these genes were considered direct or indirect targets of p50 and Bcl-3. All of the p50 gene targets were contained in the Bcl-3 gene target list. Most genes were involved with protein degradation, signaling, translation, transcription, and transport. To identify direct targets of p50 and Bcl-3 we performed chromatin immunoprecipitation of selected genes previously shown to have roles in atrophy. Trim63 (MuRF1), Fbxo32 (MAFbx), Ubc, Ctsl, Runx1, Tnfrsf12a (Tweak receptor), and Cxcl10 (IP-10) showed increased Bcl-3 binding to κB sites in unloaded muscle and thus were direct targets of Bcl-3. p50 binding to the same sites on these genes either did not change or increased, supporting the idea of p50:Bcl-3 binding complexes. p65 binding to κB sites showed decreased or no binding to these genes with unloading. Fbxo9, Psma6, Psmc4, Psmg4, Foxo3, Ankrd1 (CARP), and Eif4ebp1 did not show changes in p65, p50, or Bcl-3 binding to κB sites, and so were considered indirect targets of p50 and Bcl-3. This work represents the first study to use a global approach to identify genes required to produce the atrophied phenotype with disuse. 24 mice were used based on 4 mice per group, 3 mouse genotypes (wild type, Nfkb1-/-, Bcl3-/-) and 2 conditions (weight-bearing and unloaded).