RRC ID 67767
Author Ozawa T, Morikawa M, Morishita Y, Ogikubo K, Itoh F, Koinuma D, Nygren PÅ, Miyazono K.
Title Systemic administration of monovalent follistatin-like 3-Fc-fusion protein increases muscle mass in mice.
Journal iScience
Abstract Targeting the signaling pathway of growth differentiation factor 8 (GDF8), also known as myostatin, has been regarded as a promising strategy to increase muscle mass in the elderly and in patients. Accumulating evidence in animal models and clinical trials has indicated that a rational approach is to inhibit a limited number of transforming growth factor β (TGF-β) family ligands, including GDF8 and activin A, without affecting other members. Here, we focused on one of the endogenous antagonists against TGF-β family ligands, follistatin-like 3 (FSTL3), which mainly binds and neutralizes activins, GDF8, and GDF11. Although bivalent human FSTL3 Fc-fusion protein was rapidly cleared from mouse circulation similar to follistatin (FST)-Fc, monovalent FSTL3-Fc (mono-FSTL3-Fc) generated with the knobs-into-holes technology exhibited longer serum half-life. Systemic administration of mono-FSTL3-Fc in mice induced muscle fiber hypertrophy and increased muscle mass in vivo. Our results indicate that the monovalent FSTL3-based therapy overcomes the difficulties of current anti-GDF8 therapies.
Volume 24(5)
Pages 102488
Published 2021-5-21
DOI 10.1016/j.isci.2021.102488
PII S2589-0042(21)00456-9
PMID 34113826
PMC PMC8170004
IF 4.447
Resource
DNA material CSII-EF-RfA (RDB04387) CSII-CA-MCS-IRES-Puro (RDB19592) CSII-CA-MCS-IRES-Hyg (RDB19593)