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Myostatin as a Putative Downstream Gene Target of Calcineurin Signaling Associated with Muscle Growth Remodeling
Author(s) -
Muthuri Stella K,
Chin Eva R,
Michel Robin N
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a1207-c
Subject(s) - myostatin , nfat , calcineurin , endocrinology , medicine , biology , muscle hypertrophy , transgene , skeletal muscle , genetically modified mouse , transcription factor , gene isoform , messenger rna , growth factor , transforming growth factor , signal transduction , gene expression , microbiology and biotechnology , receptor , gene , transplantation , genetics
Myostatin (Mstn) is a TGFβ family growth factor that negatively regulates skeletal muscle growth with its inhibition shown to cause marked increases in muscle size. We investigated a plausible role for calcineurin (Cn), a Ca2+/calmodulin‐regulated phosphatase implicated in compensatory growth remodeling, in the regulation of Mstn using transgenic approaches that induced either constitutive activation or interference of Cn signaling. Mstn mRNA levels were lower in the muscles of transgenic mice displaying compromised Cn activity and higher in transgenic mice with enhanced Cn activity compared to wild‐type mice. Chronic administration of pharmacological Cn inhibitors CsA or FK506 to mice resulted in lower muscle Mstn mRNA levels. RT‐PCR revealed higher muscle mRNA expression of CnA β and γ isoforms in Mstn−/− mice perhaps as a compensatory response. Immunoflorescence labeling of muscle cross‐sections showed more intense fiber decorating of the Cn target transcription factor NFATc1 in Mstn−/− mice compared to wild‐type controls. These results suggest that myostatin may be a downstream target gene of Cn signaling in a manner associated with muscle growth remodeling and may itself regulate levels of Cn expression. (Funded by NSERC, CIHR and CRC to RNM)