한빛사 논문
Abstract
*Department of Molecular Biology and Genetics, The Johns Hopkins
University School of Medicine, 725 North Wolfe Street, PCTB 803, Baltimore, MD
21205; †Wyeth Exploratory
Drug Safety, One Burtt Road, Andover, MA 01810; §Antibody Technology Group, ¶Department of
Cardiovascular and Metabolic Diseases, and ||Department of
Inflammation, Wyeth Discovery Research, 200 Cambridge Park Drive, Cambridge, MA
02140; **MetaMorphix, Canada, 343-111 Research Drive, Saskatoon, SK,
Canada S7N 3R2; ††MetaMorphix, Inc., 8000 Virginia Manor Road, Suite
140, Beltsville, MD 20705; ‡‡Departments of Pathology, Molecular
and Human Genetics, and Molecular and Cellular Biology, and Program in
Developmental Biology, Baylor College of Medicine, Houston, TX 77030; and
§§Cardiovascular Research Center, Massachusetts General
Hospital, Department of Medicine, Harvard Medical School, 13th Street,
Charlestown, MA 02139
Edited by Eric N. Olson, University of Texas Southwestern Medical Center, Dallas, TX, and approved October 24, 2005 (received for review July 15, 2005)
Myostatin is a secreted protein that normally functions as a negative regulator of muscle growth. Agents capable of blocking the myostatin signaling pathway could have important applications for treating human muscle degenerative diseases as well as for enhancing livestock production. Here we describe a potent myostatin inhibitor, a soluble form of the activin type IIB receptor (ACVR2B), which can cause dramatic increases in muscle mass (up to 60% in 2 weeks) when injected into wild-type mice. Furthermore, we show that the effect of the soluble receptor is attenuated but not eliminated in Mstn-/- mice, suggesting that at least one other ligand in addition to myostatin normally functions to limit muscle growth. Finally, we provide genetic evidence that these ligands signal through both activin type II receptors, ACVR2 and ACVR2B, to regulate muscle growth in vivo.
Author contributions: S.-J.L., L.A.R., M.V.D., S.G., M.E.P.G., K.N.T., J.F.W., L.-f.L., E.Q., R.L.S., and N.M.W. designed research; S.-J.L., L.A.R., M.V.D., S.G., M.E.P.G., K.N.T., J.F.W., C.B., G.E., J.H., B.T., B.G., M.-S.J., S.M.S., and L.-f.L. performed research; L.A.R., M.V.D., S.G., M.E.P.G., K.N.T., J.F.W., C.B., G.E., J.H., B.T., B.G., M.-S.J., M.M., E.L., and L.-f.L. contributed new reagents/analytic tools; S.-J.L. analyzed data; and S.-J.L. and N.M.W. wrote the paper.
Conflict of interest statement: Myostatin was licensed by The Johns Hopkins University to MetaMorphix and sublicensed to Wyeth. S.-J.L. is entitled to a share of sales royalty received by The Johns Hopkins University from sales of this factor. The Johns Hopkins University and S.-J.L. also own MetaMorphix stock, which is subject to certain restrictions under university policy. S.-J.L. is a paid consultant to MetaMorphix. The terms of these arrangements are being managed by the university in accordance with its conflict of interest policies.
Freely available online through the PNAS open access option.
†To whom correspondence should be addressed.
¶¶Present address: Novartis Institutes for BioMedical Research, Models of Disease Center, 250 Massachusetts Avenue, Cambridge, MA 02139.
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