Relative roles of TGF‐β1 and Wnt in the systemic regulation and aging of satellite cell responses

Abstract

Summary Muscle stem (satellite) cells are relatively resistant to cell‐autonomous aging. Instead, their endogenous signaling profile and regenerative capacity is strongly influenced by the aged P‐Smad3, differentiated niche, and by the aged circulation. With respect to muscle fibers, we previously established that a shift from active Notch to excessive transforming growth factor‐beta (TGF‐β) induces CDK inhibitors in satellite cells, thereby interfering with productive myogenic responses. In contrast, the systemic inhibitor of muscle repair, elevated in old sera, was suggested to be Wnt. Here, we examined the age‐dependent myogenic activity of sera TGF‐β1, and its potential cross‐talk with systemic Wnt. We found that sera TGF‐β1 becomes elevated within aged humans and mice, while systemic Wnt remained undetectable in these species. Wnt also failed to inhibit satellite cell myogenicity, while TGF‐β1 suppressed regenerative potential in a biphasic fashion. Intriguingly, young levels of TGF‐β1 were inhibitory and young sera suppressed myogenesis if TGF‐β1 was activated. Our data suggest that platelet‐derived sera TGF‐β1 levels, or endocrine TGF‐β1 levels, do not explain the age‐dependent inhibition of muscle regeneration by this cytokine. In vivo , TGF‐β neutralizing antibody, or a soluble decoy, failed to reduce systemic TGF‐β1 and rescue myogenesis in old mice. However, muscle regeneration was improved by the systemic delivery of a TGF‐β receptor kinase inhibitor, which attenuated TGF‐β signaling in skeletal muscle. Summarily, these findings argue against the endocrine path of a TGF‐β1‐dependent block on muscle regeneration, identify physiological modalities of age‐imposed changes in TGF‐β1, and introduce new therapeutic strategies for the broad restoration of aged organ repair.

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References 61

1. 1.

   Abe M, Harpel JG, Metz CN, Nunes I, Loskutoff DJ, Rifkin DB. An assay for transforming growth factor-beta using cells transfected with a plasminogen activator inhibitor-1 promoter-luciferase construct. Anal. Biochem. 1994;216:276-284.

   Not in our library10.1006/abio.1994.1042

2. 2.

   Andrews ZB, Zhao H, Frugier T, Meguro R, Grattan DR, Koishi K, McLennan IS. Transforming growth factor beta2 haploinsufficient mice develop age-related nigrostriatal dopamine deficits. Neurobiol. Dis. 2006;21:568-575.

   Not in our library10.1016/j.nbd.2005.09.001

3. 3.

   Annes JP, Munger JS, Rifkin DB. Making sense of latent TGFbeta activation. J. Cell Sci. 2003;116:217-224.

   Not in our library10.1242/jcs.00229

4. 4.

   Assoian RK, Komoriya A, Meyers CA, Miller DM, Sporn MB. Transforming growth factor-beta in human platelets. Identification of a major storage site, purification, and characterization. J. Biol. Chem. 1983;258:7155-7160.

   Not in our library

5. 5.

   Bonyadi M, Rusholme SA, Cousins FM, Su HC, Biron CA, Farrall M, Akhurst RJ. Mapping of a major genetic modifier of embryonic lethality in TGF beta 1 knockout mice. Nat. Genet. 1997;15:207-211.

   Not in our library10.1038/ng0297-207

6. 6.

   Brack AS, Rando TA. Intrinsic changes and extrinsic influences of myogenic stem cell function during aging. Stem Cell Rev. 2007;3:226-237.

   Not in our library10.1007/s12015-007-9000-2

7. 7.

   Brack AS, Conboy MJ, Roy S, Lee M, Kuo CJ, Keller C, Rando TA. Increased Wnt signaling during aging alters muscle stem cell fate and increases fibrosis. Science (New York, NY). 2007;317:807-810.

   Not in our library10.1126/science.1144090

8. 8.

   Brack AS, Conboy IM, Conboy MJ, Shen J, Rando TA. A temporal switch from notch to Wnt signaling in muscle stem cells is necessary for normal adult myogenesis. Cell Stem Cell. 2008;2:50-59.

   Not in our library10.1016/j.stem.2007.10.006

9. 9.

   Brand T, MacLellan WR, Schneider MD. A dominant-negative receptor for type beta transforming growth factors created by deletion of the kinase domain. J. Biol. Chem. 1993;268:11500-11503.

   Not in our library

10. 10.

    Brionne TC, Tesseur I, Masliah E, Wyss-Coray T. Loss of TGF-beta 1 leads to increased neuronal cell death and microgliosis in mouse brain. Neuron. 2003;40:1133-1145.

    Not in our library10.1016/s0896-6273(03)00766-9

11. 11.
    Loss of stem cell regenerative capacity within aged niches · 2007

    No notice
12. 12.

    Carlson ME, Conboy IM. Regulating the Notch pathway in embryonic, adult and old stem cells. Curr. Opin. Pharmacol. 2007b;7:303-309.

    Not in our library10.1016/j.coph.2007.02.004

13. 13.

    Carlson BM, Faulkner JA. Muscle transplantation between young and old rats: age of host determines recovery. Am. J. Physiol. 1989;256:C1262-C1266.

    Not in our library10.1152/ajpcell.1989.256.6.c1262

14. 14.

    Carlson ME, Hsu M, Conboy IM. Imbalance between pSmad3 and Notch induces CDK inhibitors in old muscle stem cells. Nature. 2008;454:528-532.

    Not in our library10.1038/nature07034

15. 15.

    Collins CA, Olsen I, Zammit PS, Heslop L, Petrie A, Partridge TA, Morgan JE. Stem cell function, self-renewal, and behavioral heterogeneity of cells from the adult muscle satellite cell niche. Cell. 2005;122:289-301.

    Not in our library10.1016/j.cell.2005.05.010

16. 16.

    Conboy IM, Rando TA. The regulation of Notch signaling controls satellite cell activation and cell fate determination in postnatal myogenesis. Dev. Cell. 2002;3:397-409.

    Not in our library10.1016/s1534-5807(02)00254-x

17. 17.

    Conboy IM, Conboy MJ, Smythe GM, Rando TA. Notch-mediated restoration of regenerative potential to aged muscle. Science (New York, NY). 2003;302:1575-1577.

    Not in our library10.1126/science.1087573

18. 18.

    Conboy IM, Conboy MJ, Wagers AJ, Girma ER, Weissman IL, Rando TA. Rejuvenation of aged progenitor cells by exposure to a young systemic environment. Nature. 2005;433:760-764.

    Not in our library10.1038/nature03260

19. 19.

    Danielpour D, Kim KY, Dart LL, Watanabe S, Roberts AB, Sporn MB. Sandwich enzyme-linked immunosorbent assays (SELISAs) quantitate and distinguish two forms of transforming growth factor-beta (TGF-beta 1 and TGF-beta 2) in complex biological fluids. Growth Factors. 1989;2:61-71.

    Not in our library10.3109/08977198909069082

20. 20.

    Datto MB, Frederick JP, Pan L, Borton AJ, Zhuang Y, Wang XF. Targeted disruption of Smad3 reveals an essential role in transforming growth factor beta-mediated signal transduction. Mol. Cell. Biol. 1999;19:2495-2504.

    Not in our library10.1128/mcb.19.4.2495

21. 21.

    Derynck R, Zhang YE. Smad-dependent and Smad-independent pathways in TGF-beta family signalling. Nature. 2003;425:577-584.

    Not in our library10.1038/nature02006

22. 22.

    Dorshkind K, Montecino-Rodriguez E, Signer RA. The ageing immune system: is it ever too old to become young again? Nat. Rev. 2009;9:57-62.

    Not in our library10.1038/nri2471

23. 23.

    Dunker N, Krieglstein K. Targeted mutations of transforming growth factor-beta genes reveal important roles in mouse development and adult homeostasis. Eur. J. Biochem. 2000;267:6982-6988.

    Not in our library10.1046/j.1432-1327.2000.01825.x

24. 24.

    Feng XH, Derynck R. Specificity and versatility in TGF-beta signaling through Smads. Annu. Rev. Cell Dev. Biol. 2005;21:659-693.

    Not in our library10.1146/annurev.cellbio.21.022404.142018

25. 25.

    Gellibert F, Woolven J, Fouchet MH, Mathews N, Goodland H, Lovegrove V, Laroze A, Nguyen VL, Sautet S, Wang R, Janson C, Smith W, Krysa G, Boullay V, De Gouville AC, Huet S, Hartley D. Identification of 1,5-naphthyridine derivatives as a novel series of potent and selective TGF-beta type I receptor inhibitors. J. Med. Chem. 2004;47:4494-4506.

    Not in our library10.1021/jm0400247

26. 26.

    Grounds MD. Age-associated changes in the response of skeletal muscle cells to exercise and regeneration. Ann. N. Y. Acad. Sci. 1998;854:78-91.

    Not in our library10.1111/j.1749-6632.1998.tb09894.x

27. 27.

    Grounds MD. Reasons for the degeneration of ageing skeletal muscle: a central role for IGF-1 signalling. Biogerontology. 2002;3:19-24.

    Not in our library10.1023/a:1015234709314

28. 28.

    Hyytiainen M, Penttinen C, Keski-Oja J. Latent TGF-beta binding proteins: extracellular matrix association and roles in TGF-beta activation. Crit. Rev. Clin. Lab. Sci. 2004;41:233-264.

    Not in our library10.1080/10408360490460933

29. 29.

    Ignowski JM, Schaffer DV. Kinetic analysis and modeling of firefly luciferase as a quantitative reporter gene in live mammalian cells. Biotechnol. Bioeng. 2004;86:827-834.

    Not in our library10.1002/bit.20059

30. 30.

    Ikeya M, Takada S. Wnt signaling from the dorsal neural tube is required for the formation of the medial dermomyotome. Development (Cambridge, England). 1998;125:4969-4976.

    Not in our library10.1242/dev.125.24.4969

31. 31.

    Itoh S, Thorikay M, Kowanetz M, Moustakas A, Itoh F, Heldin CH, ten Dijke P. Elucidation of Smad requirement in transforming growth factor-beta type I receptor-induced responses. J. Biol. Chem. 2003;278:3751-3761.

    Not in our library10.1074/jbc.m208258200

32. 32.

    Kamanga-Sollo E, Pampusch MS, White ME, Dayton WR. Role of insulin-like growth factor binding protein (IGFBP)-3 in TGF-beta- and GDF-8 (myostatin)-induced suppression of proliferation in porcine embryonic myogenic cell cultures. J. Cell. Physiol. 2003;197:225-231.

    Not in our library10.1002/jcp.10362

33. 33.

    Kaykas A, Yang-Snyder J, Heroux M, Shah KV, Bouvier M, Moon RT. Mutant Frizzled 4 associated with vitreoretinopathy traps wild-type Frizzled in the endoplasmic reticulum by oligomerization. Nat. Cell Biol. 2004;6:52-58.

    Not in our library10.1038/ncb1081

34. 34.

    Kundu SD, Kim IY, Yang T, Doglio L, Lang S, Zhang X, Buttyan R, Kim SJ, Chang J, Cai X, Wang Z, Lee C. Absence of proximal duct apoptosis in the ventral prostate of transgenic mice carrying the C3(1)-TGF-beta type II dominant negative receptor. Prostate. 2000;43:118-124.

    Not in our library10.1002/(sici)1097-0045(20000501)43:2<118::aid-pros6>3.0.co;2-v

35. 35.

    Larsson J, Goumans MJ, Sjostrand LJ, van Rooijen MA, Ward D, Leveen P, Xu X, ten Dijke P, Mummery CL, Karlsson S. Abnormal angiogenesis but intact hematopoietic potential in TGF-beta type I receptor-deficient mice. EMBO J. 2001;20:1663-1673.

    Not in our library10.1093/emboj/20.7.1663

36. 36.

    Le Grand F, Jones AE, Seale V, Scime A, Rudnicki MA. Wnt7a activates the planar cell polarity pathway to drive the symmetric expansion of satellite stem cells. Cell stem cell. 2009;4:535-547.

    Not in our library10.1016/j.stem.2009.03.013

37. 37.

    Li Y, Foster W, Deasy BM, Chan Y, Prisk V, Tang Y, Cummins J, Huard J. Transforming growth factor-beta1 induces the differentiation of myogenic cells into fibrotic cells in injured skeletal muscle: a key event in muscle fibrogenesis. Am. J. Pathol. 2004;164:1007-1019.

    Not in our library10.1016/s0002-9440(10)63188-4

38. 38.

    Marom K, Fainsod A, Steinbeisser H. Patterning of the mesoderm involves several threshold responses to BMP-4 and Xwnt-8. Mech. Dev. 1999;87:33-44.

    Not in our library10.1016/s0925-4773(99)00137-9

39. 39.

    Massague J. The TGF-beta family of growth and differentiation factors. Cell. 1987;49:437-438.

    Not in our library10.1016/0092-8674(87)90443-0

40. 40.

    Massague J. TGF-beta signal transduction. Annu. Rev. Biochem. 1998;67:753-791.

    Not in our library10.1146/annurev.biochem.67.1.753

41. 41.

    Massague J, Chen YG. Controlling TGF-beta signaling. Genes Dev. 2000;14:627-644.

    Not in our library

42. 42.

    Mauro A. Satellite cell of skeletal muscle fibers. J. Biophys. Biochem. Cytol. 1961;9:493-495.

    Not in our library10.1083/jcb.9.2.493

43. 43.

    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.

    Not in our library10.1038/387083a0

44. 44.

    Moresi V, Pristera A, Scicchitano BM, Molinaro M, Teodori L, Sassoon D, Adamo S, Coletti D. Tumor necrosis factor-alpha inhibition of skeletal muscle regeneration is mediated by a caspase-dependent stem cell response. Stem cells (Dayton, Ohio). 2008;26:997-1008.

    Not in our library10.1634/stemcells.2007-0493

45. 45.

    Muller B, Hartmann B, Pyrowolakis G, Affolter M, Basler K. Conversion of an extracellular Dpp/BMP morphogen gradient into an inverse transcriptional gradient. Cell. 2003;113:221-233.

    Not in our library10.1016/s0092-8674(03)00241-1

46. 46.

    Oshima M, Oshima H, Taketo MM. TGF-beta receptor type II deficiency results in defects of yolk sac hematopoiesis and vasculogenesis. Dev. Biol. 1996;179:297-302.

    Not in our library10.1006/dbio.1996.0259

47. 47.

    Renault V, Thornell LE, Eriksson PO, Butler-Browne G, Mouly V. Regenerative potential of human skeletal muscle during aging. Aging Cell. 2002;1:132-139.

    Not in our library10.1046/j.1474-9728.2002.00017.x

48. 48.

    Schultz E, Lipton BH. Skeletal muscle satellite cells: changes in proliferation potential as a function of age. Mech. Ageing Dev. 1982;20:377-383.

    Not in our library10.1016/0047-6374(82)90105-1

49. 49.

    Shah AH, Tabayoyong WB, Kimm SY, Kim SJ, Van Parijs L, Lee C. Reconstitution of lethally irradiated adult mice with dominant negative TGF-beta type II receptor-transduced bone marrow leads to myeloid expansion and inflammatory disease. J. Immunol. 2002;169:3485-3491.

    Not in our library10.4049/jimmunol.169.7.3485

50. 50.

    Shen W, Li Y, Zhu J, Schwendener R, Huard J. Interaction between macrophages, TGF-beta1, and the COX-2 pathway during the inflammatory phase of skeletal muscle healing after injury. J. Cell. Physiol. 2008;214:405-412.

    Not in our library10.1002/jcp.21212

51. 51.

    Sherwood RI, Christensen JL, Conboy IM, Conboy MJ, Rando TA, Weissman IL, Wagers AJ. Isolation of adult mouse myogenic progenitors: functional heterogeneity of cells within and engrafting skeletal muscle. Cell. 2004;119:543-554.

    Not in our library10.1016/j.cell.2004.10.021

52. 52.

    Shi DL, Bourdelas A, Umbhauer M, Boucaut JC. Zygotic Wnt/beta-catenin signaling preferentially regulates the expression of Myf5 gene in the mesoderm of Xenopus. Dev. Biol. 2002;245:124-135.

    Not in our library10.1006/dbio.2002.0633

53. 53.

    Singh J, Chuaqui CE, Boriack-Sjodin PA, Lee WC, Pontz T, Corbley MJ, Cheung HK, Arduini RM, Mead JN, Newman MN, Papadatos JL, Bowes S, Josiah S, Ling LE. Successful shape-based virtual screening: the discovery of a potent inhibitor of the type I TGFbeta receptor kinase (TbetaRI). Bioorg. Med. Chem. Lett. 2003;13:4355-4359.

    Not in our library10.1016/j.bmcl.2003.09.028

54. 54.

    Tang P, Jasser SA, Sung JC, Shi Y, Steck PA, Yung WK. Transforming growth factor-alpha antisense vectors can inhibit glioma cell growth. J. Neurooncol. 1999;43:127-135.

    Not in our library10.1023/a:1006272019933

55. 55.

    Wagers AJ, Conboy IM. Cellular and molecular signatures of muscle regeneration: current concepts and controversies in adult myogenesis. Cell. 2005;122:659-667.

    Not in our library10.1016/j.cell.2005.08.021

56. 56.

    Wagner J, Schmidt C, Nikowits W, Christ B. Compartmentalization of the somite and myogenesis in chick embryos are influenced by wnt expression. Dev. Biol. 2000;228:86-94.

    Not in our library10.1006/dbio.2000.9921

57. 57.

    Wharton SJ, Basu SP, Ashe HL. Smad affinity can direct distinct readouts of the embryonic extracellular Dpp gradient in Drosophila. Curr. Biol. 2004;14:1550-1558.

    Not in our library10.1016/j.cub.2004.08.053

58. 58.

    Wyss-Coray T, Borrow P, Brooker MJ, Mucke L. Astroglial overproduction of TGF-beta 1 enhances inflammatory central nervous system disease in transgenic mice. J. Neuroimmunol. 1997;77:45-50.

    Not in our library10.1016/s0165-5728(97)00049-0

59. 59.

    Wyss-Coray T, Lin C, Yan F, Yu GQ, Rohde M, McConlogue L, Masliah E, Mucke L. TGF-beta1 promotes microglial amyloid-beta clearance and reduces plaque burden in transgenic mice. Nat. Med. 2001;7:612-618.

    Not in our library10.1038/87945

60. 60.

    Yang X, Letterio JJ, Lechleider RJ, Chen L, Hayman R, Gu H, Roberts AB, Deng C. Targeted disruption of SMAD3 results in impaired mucosal immunity and diminished T cell responsiveness to TGF-beta. EMBO J. 1999;18:1280-1291.

    Not in our library10.1093/emboj/18.5.1280

61. 61.

    Yu JH, Schaffer DV. High-throughput, library-based selection of a murine le0ukemia virus variant to infect nondividing cells. J. Virol. 2006;80:8981-8988.

    Not in our library10.1128/jvi.00615-06

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