Gene expression profiling of skeletal muscles treated with a soluble activin type IIB receptor

Fedik Rahimov, Oliver D. King, Leigh C. Warsing, Rachel E. Powell, Charles P. Emerson, Louis M. Kunkel, Kathryn R. Wagner

Research output: Contribution to journalArticlepeer-review

33 Scopus citations


Inhibition of the myostatin signaling pathway is emerging as a promising therapeutic means to treat muscle wasting and degenerative disorders. Activin type IIB receptor (ActRIIB) is the putative myostatin receptor, and a soluble activin receptor (ActRIIB-Fc) has been demonstrated to potently inhibit a subset of transforming growth factor (TGF)-β family members including myostatin. To determine reliable and valid biomarkers for ActRIIB-Fc treatment, we assessed gene expression profiles for quadriceps muscles from mice treated with ActRIIB-Fc compared with mice genetically lacking myostatin and control mice. Expression of 134 genes was significantly altered in mice treated with ActRIIB- Fc over a 2-wk period relative to control mice (fold change < 1.5, P > 0.001), whereas the number of significantly altered genes in mice treated for 2 days was 38, demonstrating a time-dependent response to ActRIIB-Fc in overall muscle gene expression. The number of significantly altered genes in Mstn-/- mice relative to control mice was substantially higher (360), but for most of these genes the expression levels in the 2-wk treated mice were closer to the levels in the Mstn-/- mice than in control mice (P > 1030). Expression levels of 30 selected genes were further validated with quantitative real-time polymerase chain reaction (qPCR), and a correlation of ≥0.89 was observed between the fold changes from the microarray analysis and the qPCR analysis. These data suggest that treatment with ActRIIB-Fc results in overlapping but distinct gene expression signatures compared with myostatin genetic mutation. Differentially expressed genes identified in this study can be used as potential biomarkers for ActRIIB-Fc treatment, which is currently in clinical trials as a therapeutic agent for muscle wasting and degenerative disorders.

Original languageEnglish (US)
Pages (from-to)398-407
Number of pages10
JournalPhysiological Genomics
Issue number8
StatePublished - 2011


  • Actriib-fc
  • Myostatin

ASJC Scopus subject areas

  • Physiology
  • Genetics


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