RGD Reference Report - Muscle myostatin signalling is enhanced in experimental cancer cachexia. - Rat Genome Database

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Muscle myostatin signalling is enhanced in experimental cancer cachexia.

Authors: Costelli, P  Muscaritoli, M  Bonetto, A  Penna, F  Reffo, P  Bossola, M  Bonelli, G  Doglietto, GB  Baccino, FM  Rossi Fanelli, F 
Citation: Costelli P, etal., Eur J Clin Invest. 2008 Jul;38(7):531-8.
RGD ID: 2303552
Pubmed: PMID:18578694   (View Abstract at PubMed)
DOI: DOI:10.1111/j.1365-2362.2008.01970.x   (Journal Full-text)

BACKGROUND/AIMS: Myostatin belongs to the transforming growth factor-beta superfamily and negatively regulates skeletal muscle mass. Its deletion induces muscle overgrowth, while, on the contrary, its overexpression or systemic administration cause muscle atrophy. The present study was aimed at investigating whether muscle depletion as occurring in an experimental model of cancer cachexia, the rat bearing the Yoshida AH-130 hepatoma, is associated with modulations of myostatin signalling and whether the cytokine tumour necrosis factor-alpha may be relevant in this regard. MATERIALS AND METHODS: Protein levels of myostatin, follistatin (myostatin endogenous inhibitor) and the activin receptor type IIB have been evaluated in the gastrocnemius of tumour-bearing rats by Western blotting. Circulating myostatin and follistatin in tumour hosts were evaluated by immunoprecipitation, while the DNA-binding activity of the SMAD transcription factors was determined by electrophoretic-mobility shift assay. RESULTS: In day 4 tumour hosts muscle myostatin levels were comparable to controls, yet follistatin was reduced, and SMAD DNA-binding activity was enhanced. At day 7, both myostatin and follistatin increased in tumour bearers, while SMAD DNA-binding activity was unchanged. To investigate whether tumour necrosis factor-alpha contributed to induce such changes, rats were administered pentoxifylline, an inhibitor of tumour necrosis factor-alpha synthesis that partially corrects muscle depletion in tumour-bearing rats. The drug reduced both myostatin expression and SMAD DNA-binding activity in day 4 tumour hosts and up-regulated follistatin at day 7. CONCLUSIONS: These observations suggest that myostatin pathway should be regarded as a potential therapeutic target in cancer cachexia.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
MSTNHumanCachexia  ISOMstn (Rattus norvegicus)associated with Carcinoma more ...RGD 
MstnRatCachexia  IEP associated with Carcinoma more ...RGD 
MstnMouseCachexia  ISOMstn (Rattus norvegicus)associated with Carcinoma more ...RGD 

Objects Annotated

Genes (Rattus norvegicus)
Mstn  (myostatin)

Genes (Mus musculus)
Mstn  (myostatin)

Genes (Homo sapiens)
MSTN  (myostatin)


Additional Information