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| Status |
Public on Apr 30, 2009 |
| Title |
Smad2 and 3 transcription factors control muscle mass in adulthood |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
Loss of muscle mass occurs in a variety of diseases including cancer, chronic heart failure, AIDS, diabetes and renal failure, often aggravating pathological progression. Preventing muscle wasting by promoting muscle growth has been proposed as a possible therapeutic approach. Myostatin is an important negative modulator of muscle growth during myogenesis and myostatin inhibitors are attractive drug targets. However, the role of the myostatin pathway in adulthood and the transcription factors involved in the signaling are unclear. Moreover recent results confirm that other TGFβ members control muscle mass. Using genetic tools we perturbed this pathway in adult myofibers, in vivo, to characterize the downstream targets and their ability to control muscle mass. Smad2 and Smad3 are the transcription factors downstream of myostatin/TGFβ and induce an atrophy program which is MuRF1 independent and requires FoxO activity. Furthermore Smad2/3 inhibition promotes muscle hypertrophy independent of satellite cells but partially dependent of mTOR signalling. Thus myostatin and Akt pathways cross-talk at different levels. These findings point to myostatin inhibitors as good drugs to promote muscle growth during rehabilitation especially when they are combined with IGF1-Akt activators.
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| Overall design |
Tansgenic mice were generated that express a fusion protein of Akt with the estrogen binding domain in skeletal muscle. Addition of tamoxifen stabilizes the protein leading to increased Akt signaling and muscle hypertrophy. RNA was extracted from gastrocnemius muscle after 24h oil or tamoxifen treatment or 48h tamoxifen treatment. RNA from the muscles of 3-4 mice were pooled for each chip (Affymetrix Mouse 430 2.0 whole genome expression).
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| Contributor(s) |
Sartori R, Milan G, Patron M, Mammucari C, Blaauw B, Abraham R, Sandri M |
| Citation(s) |
19357234 |
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| Submission date |
Mar 25, 2009 |
| Last update date |
Feb 11, 2019 |
| Contact name |
Reimar Abraham |
| E-mail(s) |
[email protected]
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| Organization name |
Venetian Institute of Molecular Medicine
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| Street address |
Via Orus 2
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| City |
Padova |
| ZIP/Postal code |
35129 |
| Country |
Italy |
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| Platforms (1) |
| GPL1261 |
[Mouse430_2] Affymetrix Mouse Genome 430 2.0 Array |
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| Samples (3) |
| GSM385702 |
Akt_Cre mice treated with tamoxifen for 48h upregulating Akt expression in muscle only |
| GSM386471 |
Akt_Cre mice treated with oil for 24h as a control |
| GSM386472 |
Akt_Cre mice treated with tamoxifen for 24h upregulating Akt expression in muscle only |
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| Relations |
| BioProject |
PRJNA115877 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE15397_RAW.tar |
10.5 Mb |
(http)(custom) |
TAR (of CEL, CHP) |
| Processed data included within Sample table |
| Processed data provided as supplementary file |
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