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| Status |
Public on Sep 29, 2020 |
| Title |
The vitamin D receptor (VDR) autonomously regulates skeletal muscle mass |
| Organism |
Rattus norvegicus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Vitamin D (VitD) deficiency is estimated to affect ~40% of the world’s population. Notably, VitD deficiency has been associated with impaired muscle maintenance and insulin resistance. VitD exerts its actions through the ubiquitous Vitamin D-receptor (VDR), the expression of which was recently confirmed in fully-differentiated muscle. To seek a possible autonomous role of the VDR in skeletal muscle, we first generated stable VDR-knockdown cells, which exhibited impaired myogenesis (i.e. cell-cycling, differentiation and myotube formation). In vivo VDR-knockdown in rat hind-limbs elicited myofibre atrophy and triggered autophagy pathways. In contrast, in vivo VDR-overexpression yielded myofibre hypertrophy; enhancing translational efficiency (e.g. mTOR-signaling), ribosomal biogenesis and satellite cell content. Neither VDR-knockdown nor overexpression impacted muscle glucose uptake. Crucially, induction of VDR mRNA correlated with muscle hypertrophy in humans following long-term resistance exercise training, but not aspects of insulin sensitivity. The VDR autonomously regulates muscle mass, acting reciprocally to limit atrophy and promote hypertrophy.
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| Overall design |
In vivo electroporation was used to knock out (ko) or knock in (ki) the vitmain D receptor in the tibialis anterior muscle of one hindlimb in rats. VDR-KD groups received VDR shRNA (Table S1) in right leg TAM and scramble shRNA in left leg TAM. VDR-OE groups received pCAGGS-mVDR in right leg TAM, and empty pCAGGS controls in left leg TAM. Immediately following, one HV (900 V/cm, 100 µ-sec pulse), and four LV (90 V/cm, 100 m-sec) pulses were administered across the distal limb via tweezer-electrodes attached to an ECM-830 electroporator (BTX, Holliston, MA). Animals subsequently received a subcutaneous injection of carprofen (50mg/kg), before recovery from anesthesia. RNA-seq was carried out with the contrast of interest being either ko v control limb or ki v control limb.
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| Contributor(s) |
Bass JJ, Gallagher IJ, Atherton PJ |
| Citation(s) |
32771696, 33258480 |
| Submission date |
Feb 12, 2018 |
| Last update date |
Apr 06, 2021 |
| Contact name |
Iain Gallagher |
| E-mail(s) |
iaingallagher@gmail.com
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| Phone |
00 44 1786 46 6024
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| Organization name |
University of Stirling
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| Department |
Faculty of Health Sciences and Sport
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| Street address |
Room 4B133 Cottrell Building, University of Stirling, Airthrey Road
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| City |
Stirling |
| ZIP/Postal code |
FK9 4LA |
| Country |
United Kingdom |
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| Platforms (1) |
| GPL22396 |
Illumina HiSeq 4000 (Rattus norvegicus) |
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| Samples (28)
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| Relations |
| BioProject |
PRJNA433878 |
| SRA |
SRP132733 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE110507_RAW.tar |
4.2 Mb |
(http)(custom) |
TAR (of TXT) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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