Targeting the myostatin signaling pathway to treat muscle wasting diseases

Current Opinion in Supportive and Palliative Care

Volumn 5, Issue 4, 2011, Pages 334-341

  Han, H Q ^a   Mitch, William E ^b  

^a AMGEN INC   (United States)

^b BAYLOR COLLEGE OF MEDICINE   (United States)

Author keywords

Activin A; Cancer; Chronic kidney disease; Foxo; Heart failure; Muscle protein breakdown; Muscle wasting; Myostatin; Smad; Ubiquitin proteasome system

Indexed keywords

INSULIN; MYOSTATIN; SOMATOMEDIN C;

ANIMAL; CHRONIC KIDNEY FAILURE; DISEASE MODEL; DRUG EFFECT; HUMAN; METABOLISM; MUSCLE ATROPHY; NEOPLASM; PROTEIN INTAKE; REVIEW; RISK FACTOR; SIGNAL TRANSDUCTION;

ANIMALS; DIETARY PROTEINS; DISEASE MODELS, ANIMAL; HUMANS; INSULIN; INSULIN-LIKE GROWTH FACTOR I; KIDNEY FAILURE, CHRONIC; MUSCULAR ATROPHY; MYOSTATIN; NEOPLASMS; RISK FACTORS; SIGNAL TRANSDUCTION;

EID: 84856813041     PISSN: 17514258     EISSN: 17514266     Source Type: Journal    
DOI: 10.1097/SPC.0b013e32834bddf9     Document Type: Review

References (71)

1. Anker SD, Ponikowski P, Varney S, et al. Wasting as independent risk factor for mortality in chronic heart failure. Lancet 1997; 349:1050-1053. (Pubitemid 27158249)
2. Griffiths RD. Muscle mass, survival, and the elderly ICU patient. Nutrition 1996; 12:456-458. (Pubitemid 26295088)
3. Huang CX, Tighiouart H, Beddhu S, et al. Both low muscle mass and low fat are associated with higher all-cause mortality in hemodialysis patients. Kidney Int 2010; 77:624-629.
4. Inagaki J, Rodriguez V, Bodey GP. Proceedings: Causes of death in cancer patients. Cancer 1974; 33:568-573.
5. Fouque D, Kalantar-Zadeh K, Kopple J, et al. A proposed nomenclature and diagnostic criteria for protein-energy wasting in acute and chronic kidney disease. Kidney Int 2008; 73:391-398. (Pubitemid 351186278)
6. Mitch WE. Malnutrition: A frequent misdiagnosis for hemodialysis patients. J Clin Invest 2002; 110:437-439. (Pubitemid 34919696)
7. Evans WJ, Morley JE, Argiles J, et al. Cachexia: A new definition. Clin Nutr 2008; 27:793-799.
8. Lecker SH, Goldberg AL, Mitch WE. Protein degradation by the ubiquitin- proteasome pathway in normal and disease states. J Am Soc Nephrol 2006; 17:1807-1819. (Pubitemid 44036165)
9. Lecker SH, Mitch WE. Proteolysis by the ubiquitin-proteasome system and kidney disease. J Am Soc Nephrol 2011; 22:821-824. This article reviews recent evidence for ubiquitin-proteasome pathway activation in catabolic states with special reference to kidney disease.
10. Mitch WE, Goldberg AL. Mechanisms of muscle wasting. The role of the ubiquitin-proteasome pathway. N Engl J Med 1996; 335:1897-1905. (Pubitemid 26419198)
11. Bailey JL, Zheng B, Hu Z, et al. Chronic kidney disease causes defects in signaling through the insulin receptor substrate/phosphatidylinositol 3-kinase/ Akt pathway: Implications for muscle atrophy. J Am Soc Nephrol 2006; 17:1388-1394. (Pubitemid 43673419)
12. Kortebein P, Ferrando A, Lombeida J, et al. Effect of 10 days of bed rest on skeletal muscle in healthy older adults. JAMA 2007; 297:1772-1774. (Pubitemid 46658661)
13. Hu Z, Wang H, Lee IH, et al. Endogenous glucocorticoids and impaired insulin signaling are both required to stimulate muscle wasting under pathophysiological conditions in mice. J Clin Invest 2009; 119:3059-3069.
14. Nutrition Foundation. Nitrogen balance studies after tube feeding in cancer cachexia. Nutr Rev 1956; 14:43-45.
15. Cai D, Frantz JD, Tawa NE Jr, et al. IKKbeta/NF-kappaB activation causes severe muscle wasting in mice. Cell 2004; 119:285-298. (Pubitemid 39360909)
16. Kwak KS, Zhou X, Solomon V, et al. Regulation of protein catabolism by muscle-specific and cytokine-inducible ubiquitin ligase E3alpha-II during cancer cachexia. Cancer Res 2004; 64:8193-8198. (Pubitemid 39491755)
17. Song YH, Li Y, Du J, et al. Muscle-specific expression of IGF-1 blocks angiotensin II-induced skeletal muscle wasting. J Clin Invest 2005; 115:451-458. (Pubitemid 40385487)
18. Zhang L, Du J, Hu Z, et al. IL-6 and serum amyloid A synergy mediates angiotensin II-induced muscle wasting. J Am Soc Nephrol 2009; 20:604-612.
19. Bodine SC, Latres E, Baumhueter S, et al. Identification of ubiquitin ligases required for skeletal muscle atrophy. Science 2001; 294:1704-1708. (Pubitemid 33104839)
20. Cohen S, Brault JJ, Gygi SP, et al. During muscle atrophy, thick, but not thin, filament components are degraded by MuRF1-dependent ubiquitylation. J Cell Biol 2009; 185:1083-1095.
21. Gomes MD, Lecker SH, Jagoe RT, et al. Atrogin-1, a muscle-specific F-box protein highly expressed during muscle atrophy. Proc Natl Acad Sci U S A 2001; 98:14440-14445. (Pubitemid 33121410)
22. Pickering WP, Price SR, Bircher G, et al. Nutrition in CAPD: Serum bicarbonate and the ubiquitin-proteasome system in muscle. Kidney Int 2002; 61:1286-1292. (Pubitemid 34304489)
23. Sacheck JM, Hyatt JP, Raffaello A, et al. Rapid disuse and denervation atrophy involve transcriptional changes similar to those of muscle wasting during systemic diseases. FASEB J 2007; 21:140-155. (Pubitemid 46052553)
24. Bossola M, Muscaritoli M, Costelli P, et al. Increased muscle ubiquitin mRNA levels in gastric cancer patients. Am J Physiol Regul Integr Comp Physiol 2001; 280:R1518-R1523.
25. Workeneh BT, Rondon-Berrios H, Zhang L, et al. Development of a diagnostic method for detecting increased muscle protein degradation in patients with catabolic conditions. J Am Soc Nephrol 2006; 17:3233-3239. (Pubitemid 44707785)
26. Wang H, Garzon R, Sun H, et al. NF-kappaB-YY1-miR-29 regulatory circuitry in skeletal myogenesis and rhabdomyosarcoma. Cancer Cell 2008; 14:369-381.
27. Schwarzkopf M, Coletti D, Sassoon D, Marazzi G. Muscle cachexia is regulated by a p53-PW1/Peg3-dependent pathway. Genes Dev 2006; 20:3440-3452. (Pubitemid 44969161)
28. Lee SJ. Genetic analysis of the role of proteolysis in the activation of latent myostatin. PLoS One 2008; 3:e1628.
29. McPherron AC, Lawler AM, Lee SJ. Regulation of skeletal muscle mass in mice by a new TGF-beta superfamily member. Nature 1997; 387:83-90. (Pubitemid 27202654)
30. Lee SJ, McPherron AC. Regulation of myostatin activity and muscle growth. Proc Natl Acad Sci U S A 2001; 98:9306-9311. (Pubitemid 32743912)
31. Clop A, Marcq F, Takeda H, et al. A mutation creating a potential illegitimate microRNA target site in the myostatin gene affects muscularity in sheep. Nat Genet 2006; 38:813-818. (Pubitemid 43980603)
32. McPherron AC, Lee SJ. Double muscling in cattle due to mutations in the myostatin gene. Proc Natl Acad Sci U S A 1997; 94:12457-12461. (Pubitemid 27492550)
33. Mosher DS, Quignon P, Bustamante CD, et al. A mutation in the myostatin gene increases muscle mass and enhances racing performance in heterozygote dogs. PLoS Genet 2007; 3:e79.
34. Schuelke M, Wagner KR, Stolz LE, et al. Myostatin mutation associated with gross muscle hypertrophy in a child. N Engl J Med 2004; 350:2682-2688. (Pubitemid 38788003)
35. Binns MM, Boehler DA, Lambert DH. Identification of the myostatin locus (MSTN) as having a major effect on optimum racing distance in the thoroughbred horse in the USA. Anim Genet 2010; 41 (Suppl 2):154-158.
36. Hill EW, Gu J, Eivers SS, et al. A sequence polymorphism in MSTN predicts sprinting ability and racing stamina in thoroughbred horses. PLoS One 2010; 5:e8645.
37. Yarasheski KE, Bhasin S, Sinha-Hikim I, et al. Serum myostatin- immunoreactive protein is increased in 60-92 year old women and men with muscle wasting. J Nutr Health Aging 2002; 6:343-348. (Pubitemid 36118984)
38. Reardon KA, Davis J, Kapsa RM, et al. Myostatin, insulin-like growth factor-1, and leukemia inhibitory factor mRNAs are upregulated in chronic human disuse muscle atrophy. Muscle Nerve 2001; 24:893-899. (Pubitemid 32549972)
39. Zachwieja JJ, Smith SR, Sinha-Hikim I, et al. Plasma myostatin- immunoreactive protein is increased after prolonged bed rest with low-dose T3 administration. J Gravit Physiol 1999; 6:11-15.
40. Gonzalez-Cadavid NF, Taylor WE, Yarasheski K, et al. Organization of the human myostatin gene and expression in healthy men and HIV-infected men with muscle wasting. Proc Natl Acad Sci U S A 1998; 95:14938-14943. (Pubitemid 29003735)
41. Sun DF, Chen Y, Rabkin R. Work-induced changes in skeletal muscle IGF-1 and myostatin gene expression in uremia. Kidney Int 2006; 70:453-459. (Pubitemid 44141571)
42. Breitbart A, Auger-Messier M, Molkentin JD, Heineke J. Myostatin from the heart: Local and systemic actions in cardiac failure and muscle wasting. Am J Physiol Heart Circ Physiol 2011; 300:H1973-H1982.
43. George I, Bish LT, Kamalakkannan G, et al. Myostatin activation in patients with advanced heart failure and after mechanical unloading. Eur J Heart Fail 2010; 12:444-453. This article documents that myostatin expression levels were elevated in patients with advanced heart failure.
44. Gruson D, Ahn SA, Ketelslegers JM, Rousseau MF. Increased plasma myostatin in heart failure. Eur J Heart Fail 2011; 13:734-736.
45. Costelli P, Muscaritoli M, Bonetto A, et al. Muscle myostatin signalling is enhanced in experimental cancer cachexia. Eur J Clin Invest 2008; 38:531-538. (Pubitemid 351832040)
46. Zhou X, Wang JL, Lu J, et al. Reversal of cancer cachexia and muscle wasting by ActRIIB antagonism leads to prolonged survival. Cell 2010; 142:531-543. This article reveals that in several models of cancer cachexia, pharmacological blockade of myostatin/activin-ActRIIB signaling pathway not only prevents muscle further wasting, but also reverses pre-existent loss of skeletal muscle and cardiac atrophy, thereby dramatically prolonging survival, even of animals in which tumor growth is not inhibited. Blocking this pathway is found to completely abolish the induction of atrophy-specific ubiquitin ligases in muscles and markedly stimulates muscle stem cell growth.
47. Zhang L, Rajan V, Lin E, et al. Pharmacological inhibition of myostatin suppresses systemic inflammation and muscle atrophy in mice with chronic kidney disease. FASEB J 2011; 25:1653-1663. This study demonstrates that in mice with CKD, pharmacological inhibition of myostatin is able to reverse muscle wasting and suppress circulating inflammatory cytokines. Myostatin antagonism is found to decrease the rate of protein degradation, increase protein synthesis in muscles, enhance satellite cell function, and improve IGF-1 intracellular signaling in CKD mice.
48. Lang CH, Silvis C, Nystrom G, Frost RA. Regulation of myostatin by glucocorticoids after thermal injury. FASEB J 2001; 15:1807-1809.
49. Ma K, Mallidis C, Bhasin S, et al. Glucocorticoid-induced skeletal muscle atrophy is associated with upregulation of myostatin gene expression. Am J Physiol Endocrinol Metab 2003; 285:E363-E371. (Pubitemid 36899710)
50. Carlson CJ, Booth FW, Gordon SE. Skeletal muscle myostatin mRNA expression is fiber-type specific and increases during hindlimb unloading. Am J Physiol 1999; 277 (2 Pt 2):R601-R606. (Pubitemid 29415132)
51. Lalani R, Bhasin S, Byhower F, et al. Myostatin and insulin-like growth factor-I and -II expression in the muscle of rats exposed to the microgravity environment of the NeuroLab space shuttle flight. J Endocrinol 2000; 167:417-428. (Pubitemid 32047548)
52. Wehling M, Cai B, Tidball JG. Modulation of myostatin expression during modified muscle use. FASEB J 2000; 14:103-110. (Pubitemid 30051528)
53. Otani T, Minami S, Yamoto M, Umesaki N. Production of activin A in hyperplasia and adenocarcinoma of the human endometrium. Gynecol Oncol 2001; 83:31-38. (Pubitemid 32959876)
54. Seder CW, Hartojo W, Lin L, et al. INHBA overexpression promotes cell proliferation and may be epigenetically regulated in esophageal adenocarcinoma. J Thorac Oncol 2009; 4:455-462.
55. Wildi S, Kleeff J, Maruyama H, et al. Overexpression of activin A in stage IV colorectal cancer. Gut 2001; 49:409-417. (Pubitemid 32802577)
56. Rydzewska-Rosolowska A, Borawski J, Mysliwiec M. Hepatocyte growth factor/activin A/follistatin system activation during hemodialysis with different low molecular weight heparins. Ren Fail 2009; 31:791-797.
57. Bjornstad JL, Neverdal NO, Vengen OA, et al. Alterations in circulating activin A, GDF-15, TGF-beta3 and MMP-2, -3, and -9 during one year of left ventricular reverse remodelling in patients operated for severe aortic stenosis. Eur J Heart Fail 2008; 10:1201-1207.
58. Yndestad A, Ueland T, Oie E, et al. Elevated levels of activin A in heart failure: Potential role in myocardial remodeling. Circulation 2004; 109:1379-1385. (Pubitemid 38387824)
59. Zimmers TA, Davies MV, Koniaris LG, et al. Induction of cachexia in mice by systemically administered myostatin. Science 2002; 296:1486-1488. (Pubitemid 34553097)
60. Kota J, Handy CR, Haidet AM, et al. Follistatin gene delivery enhances muscle growth and strength in nonhuman primates. Sci Transl Med 2009; 1:6ra15.
61. Glass DJ. Signaling pathways perturbing muscle mass. Curr Opin Clin Nutr Metab Care 2010; 13:225-229. This review describes the intracellular signaling mechanisms underlying muscle loss with special reference to the ubiquitin-proteasome pathway and the phosphatidylinositol- 3 kinase/Akt/Foxo pathway.
62. Benny Klimek ME, Aydogdu T, Link MJ, et al. Acute inhibition of myostatin-family proteins preserves skeletal muscle in mouse models of cancer cachexia. Biochem Biophys Res Commun 2010; 391:1548-1554. This study shows that blocking the ActRIIB (ACVR2B) signaling pathway with a decoy receptor prevents muscle atrophy and fat loss in mice bearing colon-26 adenocarcinoma and Lewis lung carcinoma.
63. Murphy KT, Chee A, Gleeson BG, et al. Antibody-directed myostatin inhibition enhances muscle mass and function in tumor-bearing mice. Am J Physiol Regul Integr Comp Physiol 2011; doi: Ajpregu.00121.2011. This study demonstrates that administration of an antimyostatin antibody attenuated muscle atrophy and loss of muscle force-producing capacity in mice bearing Lewis lung carcinoma.
64. Zhang L, Wang XH, Wang H, et al. Satellite cell dysfunction and impaired IGF-1 signaling cause CKD-induced muscle atrophy. J Am Soc Nephrol 2010; 21:419-427. This study shows that in mice with CKD, there is an impairment in IGF1/AKT signaling, which leads to protein catabolism, satellite cell dysfunction and fibrosis in muscle.
65. Anker SD, Steinborn W, Strassburg S. Cardiac cachexia. Ann Med 2004; 36:518-529. (Pubitemid 39490961)
66. Coats AJ. Origin of symptoms in patients with cachexia with special reference to weakness and shortness of breath. Int J Cardiol 2002; 85:133-139.
67. Sharma M, Kambadur R, Matthews KG, et al. Myostatin, a transforming growth factor-beta superfamily member, is expressed in heart muscle and is upregulated in cardiomyocytes after infarct. J Cell Physiol 1999; 180:1-9. (Pubitemid 29249707)
68. Shyu KG, Lu MJ, Wang BW, et al. Myostatin expression in ventricular myocardium in a rat model of volume-overload heart failure. Eur J Clin Invest 2006; 36:713-719. (Pubitemid 44393930)
69. Heineke J, Auger-Messier M, Xu J, et al. Genetic deletion of myostatin from the heart prevents skeletal muscle atrophy in heart failure. Circulation 2010; 121:419-425. This study demonstrates that heart-specific deletion of the myostatin gene in mice does not alter baseline heart size or secondarily affect skeletal muscle size, but prevents atrophy of skeletal muscle during pressure overload-induced heart failure, suggesting an endocrine role of myostatin released from myocardium in cardiac cachexia.
70. Lenk K, Erbs S, Hollriege R, et al. Exercise training leads to a reduction of elevated myostatin levels in patients with chronic heart failure. Eur J Cardiovasc Prev Rehabil 2011; doi: 10.1177/1741826711402735.
71. Lenk K, Schur R, Linke A, et al. Impact of exercise training on myostatin expression in the myocardium and skeletal muscle in a chronic heart failure model. Eur J Heart Fail 2009; 11:342-348.