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Circ Res. 2016 Apr 1;118(7):1125-41; discussion 1142. doi: 10.1161/CIRCRESAHA.116.308391.

Biochemistry and Biology of GDF11 and Myostatin: Similarities, Differences, and Questions for Future Investigation.

Author information

1
From the Department of Molecular Genetics, College of Medicine, University of Cincinnati, OH (R.G.W., T.B.T.); Department of Stem Cell and Regenerative Biology, Harvard Stem Cell Institute, Harvard University, Cambridge, MA (T.P., L.K., S.M.B., J.O., S.W., L.L.R., A.J.W., R.T.L.); Department of Neuroscience, Institut Pasteur, Paris, France (L.K.); Cardiovascular Division (T.P.), Department of Medicine, Brigham Regenerative Medicine Center, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (Y.W.F., R.T.L.); Section on Islet Cell and Regenerative Biology, Joslin Diabetes Center, Boston, MA (J.O., S.W., A.J.W.); Division of Cardiology, Universitäres Herzzentrum, Zürich, Switzerland (B.H.); Department of Medicine, University of California, San Francisco (B.H., P.G.); and Division of Cardiology, San Francisco General Hospital, CA (P.G.).
2
From the Department of Molecular Genetics, College of Medicine, University of Cincinnati, OH (R.G.W., T.B.T.); Department of Stem Cell and Regenerative Biology, Harvard Stem Cell Institute, Harvard University, Cambridge, MA (T.P., L.K., S.M.B., J.O., S.W., L.L.R., A.J.W., R.T.L.); Department of Neuroscience, Institut Pasteur, Paris, France (L.K.); Cardiovascular Division (T.P.), Department of Medicine, Brigham Regenerative Medicine Center, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (Y.W.F., R.T.L.); Section on Islet Cell and Regenerative Biology, Joslin Diabetes Center, Boston, MA (J.O., S.W., A.J.W.); Division of Cardiology, Universitäres Herzzentrum, Zürich, Switzerland (B.H.); Department of Medicine, University of California, San Francisco (B.H., P.G.); and Division of Cardiology, San Francisco General Hospital, CA (P.G.). RLee@bwh.harvard.edu amy_wagers@harvard.edu.

Abstract

Growth differentiation factor 11 (GDF11) and myostatin (or GDF8) are closely related members of the transforming growth factor β superfamily and are often perceived to serve similar or overlapping roles. Yet, despite commonalities in protein sequence, receptor utilization and signaling, accumulating evidence suggests that these 2 ligands can have distinct functions in many situations. GDF11 is essential for mammalian development and has been suggested to regulate aging of multiple tissues, whereas myostatin is a well-described negative regulator of postnatal skeletal and cardiac muscle mass and modulates metabolic processes. In this review, we discuss the biochemical regulation of GDF11 and myostatin and their functions in the heart, skeletal muscle, and brain. We also highlight recent clinical findings with respect to a potential role for GDF11 and/or myostatin in humans with heart disease. Finally, we address key outstanding questions related to GDF11 and myostatin dynamics and signaling during development, growth, and aging.

KEYWORDS:

heart disease; ligands; muscle; myocardium

PMID:
27034275
PMCID:
PMC4818972
DOI:
10.1161/CIRCRESAHA.116.308391
[Indexed for MEDLINE]
Free PMC Article

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