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Do β-Thymosins Play a Role in Human Nephrogenesis?

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Kidney Development in Renal Pathology

Part of the book series: Current Clinical Pathology ((CCPATH))

Abstract

β-Thymosins are a family of ubiquitous peptides with a molecular mass of about 5 kDa and with a sequence of 40–44 amino acid residues. The name thymosin derives from the first isolation of these peptides from calf thymus in 1966 by Goldstein et al. (Proc Natl Acad USA 56:1010–17) among other lymphocytopoietic factors. Thymosins are subdivided into three main groups according to their different isoelectric points: α-thymosins, β-thymosins, and γ-thymosins with a pH below 5.0, between 5.0 and 7.0, and above 7.0, respectively. Hannappel and coworkers first isolated Tβ4 from vertebrate’s and invertebrate’s cells through different schemes of purification. More than 15 β-thymosins were described but Tβ4 is known to be the most expressed peptide in mammalians including humans.

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References

  1. Hannappel E. β-Thymosins. Ann N Y Acad Sci. 2007;1112:21–37.

    Article  CAS  PubMed  Google Scholar 

  2. Goldstein AL, Slater FD, White A. Preparation assay and partial purification of a thymic lymphocytopoietic factor (thymosin). Proc Natl Acad Sci U S A. 1966;56:1010–17.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  3. Low TL, Goldstein AL. Chemical characterization of thymosin β4. J Biol Chem. 1982;257:1000–6.

    CAS  PubMed  Google Scholar 

  4. Hannappel E, Huff T. The thymosins–prothymosin α, parathymosin, and β-thymosin: structure and function. In: Litwack G, editor. Vitamins and hormones, vol. 66. New York: Academic; 2003. p. 257–96.

    Google Scholar 

  5. Hannappel E, Huff T, Safer D. Intracellular β-thymosins. In: Lappalainen P, editor. Actin monomer binding proteins. Austin: Landes Bioscience; 2006. p. 61–70.

    Google Scholar 

  6. Low TL, Hu SK, Goldstein AL. Complete amino acid sequence of bovine thymosin beta 4: a thymic hormone that induces terminal deoxynucleotidyl transferase activity in thymocyte populations. Proc Natl Acad Sci U S A. 1981;78:1162–6.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  7. Yang SP, Lee HJ, Su Y. Molecular cloning and structural characterization of the functional human thymosin beta4 gene. Mol Cell Biochem. 2005;272:97–105.

    Article  CAS  PubMed  Google Scholar 

  8. Low TL, Thrman GB, Chincarini C, McClure JE, Marshall GD, Hu SK, et al. Current status of thymosin research: evidence for the existence of a family of thymic factors that control T-cell maturation. Ann N Y Acad Sci. 2012;1269:131–46.

    Article  PubMed  Google Scholar 

  9. Weller FE, Mutchnick MG. Enzyme immunoassay measurement of thymosin b4. J Immunoassay. 1987;8:203–17.

    Article  CAS  PubMed  Google Scholar 

  10. Goldstein AL, Hannappel E, Sosne G, Kleinman HK. Thymosin beta4: a multifunctional regenerative peptide. Basic properties and clinical applications. Expert Opin Biol Ther. 2012;12:37–51.

    Article  CAS  PubMed  Google Scholar 

  11. Sanders MC, Goldstein AL, Wang YL. Thymosin beta 4 (Fx peptide) is a potent regulator of actin polymerization in living cells. Proc Natl Acad Sci U S A. 1992;89:4678–82.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  12. Rebar RW, Miyake A, Low TL, Goldstein AL. Thymosin stimulates secretion of luteinizing hormone-releasing factor. Science. 1981;214:669–71.

    Article  CAS  PubMed  Google Scholar 

  13. Grillon C, Rieger K, Bakal J, Schott D, Morgat JL, Hannappel E, et al. Involvement of thymosin beta 4 and endoproteinase Asp-N in the biosynthesis of the tetrapeptide AcSerAspLysPro a regulator of the hematopoietic system. FEBS Lett. 1990;274:30–4.

    Article  CAS  PubMed  Google Scholar 

  14. Lenfant M, Wdzieczak-Bakala J, Guittet E, Prome JC, Sotty D, Frindel E. Inhibitor of hematopoietic pluripotent stem cell proliferation: purification and determination of its structure. Proc Natl Acad Sci U S A. 1989;86:779–82.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  15. Sosne G, Qiu P, Goldstein AL, Wheater M. Biological activities of thymosin beta4 defined by active sites in short peptide sequences. FASEB J. 2010;24:2144–51.

    Article  CAS  PubMed  Google Scholar 

  16. Koutrafouri V, Leondiadis L, Avgoustakis K, Livaniou E, Czarnecki J, Ithakissios DS, et al. Effect of thymosin peptides on the chick chorioallantoic membrane angiogenesis model. Biochim Biophys Acta. 2001;1568:60–6.

    Article  CAS  PubMed  Google Scholar 

  17. Malinda KM, Sidhu GS, Mani H, Banaudha K, Maheshwari RK, et al. Thymosin beta4 accelerates wound healing. J Invest Dermatol. 1999;113:364–8.

    Article  CAS  PubMed  Google Scholar 

  18. Badamchian M, Fagarasan MO, Danner RL, Suffredini AF, Damavandy H, Goldstein AL. Thymosin beta(4) reduces lethality and down-regulates inflammatory mediators in endotoxin-induced septic shock. Int Immunopharmacol. 2003;3:1225–33.

    Article  CAS  PubMed  Google Scholar 

  19. Bock-Marquette I, Saxena A, White MD, Dimaio JM, Srivastava D. Thymosin beta4 activates integrin-linked kinase and promotes cardiac cell migration, survival and cardiac repair. Nature. 2004;432:466–72.

    Article  CAS  PubMed  Google Scholar 

  20. Smart N, Risebro CA, Melville AA, Moses K, Schwartz RJ, Chien KR, et al. Thymosin beta4 induces adult epicardial progenitor mobilization and neovascularization. Nature. 2007;445:177–82.

    Article  CAS  PubMed  Google Scholar 

  21. Badamchian M, Damavandy AA, Damavandy H, Wadhwa SD, Katz B, Goldstein AL. Identification and quantification of thymosin beta4 in human saliva and tears. Ann N Y Acad Sci. 2007;1112:458–65.

    Article  CAS  PubMed  Google Scholar 

  22. Inzitari R, Cabras T, Pisano E, Fanali C, Manconi B, Scarano E, et al. HPLC-ESI-MS analysis of oral human fluids reveals that gingival crevicular fluid is the main source of oral thymosins beta(4) and beta(10). J Sep Sci. 2009;32:57–63.

    Article  CAS  PubMed  Google Scholar 

  23. Nemolato S, Messana I, Cabras T, Manconi B, Inzitari R, Fanali C, et al. Thymosin beta(4) and beta(10) levels in pre-term newborn oral cavity and foetal salivary glands evidence a switch of secretion during foetal development. PLoS One. 2009;4:e5109.

    Article  PubMed Central  PubMed  Google Scholar 

  24. Erickson-Viitanen S, Ruggieri S, Natalini P, Horecker BL. Thymosin beta 10, a new analog of thymosin beta 4 in mammalian tissues. Arch Biochem Biophys. 1983;225:407–13.

    Article  CAS  PubMed  Google Scholar 

  25. Yu FX, Lin SC, Morriosn-Bogoard M, Atkinson MA, Yin HL. Thymosin beta 10 and thymosin beta 4 both actin-sequestering proteins. J Biol Chem. 1993;268:502–9.

    CAS  PubMed  Google Scholar 

  26. Golla R, Philip N, Safer D, Chintapalli J, Hoffman R, Collins L, et al. Coordinate regulation of the cytoskeleton in 3 T£ cells overexpressing thymosin beta-4. Cell Motil Cytoskeleton. 1997;38:187–200.

    Article  CAS  PubMed  Google Scholar 

  27. Philp D, Nguyen M, Scheremeta B, St-Surin S, Villa AM, Orgel A, et al. Thymosin β4 increases hair growth by activation of hair follicle stem cells. FASEB J. 2004;18:385–7.

    CAS  PubMed  Google Scholar 

  28. Lee SH, Son MJ, Oh SH, Rho SB, Park K, Kim YJ, et al. Thymosin beta 10 inhibits angiogenesis and tumor growth by interfering with Ras function. Cancer Res. 2005;65:137–48.

    CAS  PubMed  Google Scholar 

  29. Mu H, Ohashi R, Yang H, Wang X, Li M, Lin P, et al. Thymosin beta 10 inhibits cell migration and capillary-like tube formation of human coronary artery endothelial cells. Cell Motil Cytoskeleton. 2006;63:222–30.

    Article  CAS  PubMed  Google Scholar 

  30. Hall AK. Thymosin beta-10 accelerates apoptosis. Cell Mol Biol Res. 1995;41:167–80.

    CAS  PubMed  Google Scholar 

  31. Santelli G, Califano D, Chiappetta G, Vento MT, Bartoli PC, Zullo F. Thymosin beta-10 gene overexpression is a general event in human carcinogenesis. Am J Pathol. 1999;155:799–804.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  32. Chiappetta G, Pentimalli F, Monaco M, Fedele M, Pasquinelli R, Pierantoni GM, et al. Thymosin beta-10 gene expression as a possible tool in the diagnosis of thyroid neoplasias. Oncol Rep. 2004;12:239–43.

    CAS  PubMed  Google Scholar 

  33. Verghese-Nikolakaki S, Apostolikas N, Livaniou E, Ithakissios DS, Evangelatos GP. Preliminary findings on the expression of thymosin beta-10 in human breast cancer. Br J Cancer. 1996;74:1441–4.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  34. Gu Y, Wang C, Wang Y, Qiu X, Wang E. Expression of thymosin beta 10 and the role in non-small cell lung cancer. Hum Pathol. 2009;40:117–24.

    Article  CAS  PubMed  Google Scholar 

  35. Hall AK. Amplification-independent overexpression of thymosin beta-10 mRNA in human renal cell carcinoma. Ren Fail. 1994;16:243–54.

    Article  CAS  PubMed  Google Scholar 

  36. Li M, Zhang Y, Zhai Q, Feurino LW, Fisher WE, Chen C, et al. Thymosin beta-10 is aberrantly expressed in pancreatic cancer and induces JNK activation. Cancer Invest. 2009;27:251–6.

    Article  PubMed Central  PubMed  Google Scholar 

  37. Gerosa C, Fanni D, Nemolato S, Locci A, Marinelli V, Cabras T, et al. Thymosin beta-10 expression in developing human kidney. J Matern Fetal Neonatal Med. 2010;23 Suppl 3:125–8.

    Article  CAS  PubMed  Google Scholar 

  38. Fanni D, Gerosa C, Nemolato S, Locci A, Marinelli V, Cabras T, et al. Thymosin beta 10 expression in developing human salivary glands. Early Hum Dev. 2011;87:779–83.

    Article  CAS  PubMed  Google Scholar 

  39. Huff T, Muller CS, Hannappel E. Thymosin beta4 is not always the main beta-thymosin in mammalian platelets. Ann N Y Acad Sci. 2007;1112:451–7.

    Article  CAS  PubMed  Google Scholar 

  40. Voisin PJ, Pardue S, Morrison-Bogorad M. Developmental characterization of thymosin b 4 and b 10 expression in enriched neuronal cultures from rat cerebella. J Neurochem. 1995;64:109–20.

    Article  CAS  PubMed  Google Scholar 

  41. Anadon R, Rodriguez Moldes I, Carpintero P, Evangelatos G, Livianou E, Leondiadis L, et al. Differential expression of thymosins b (4) and b (10) during rat cerebellum postnatal development. Brain Res. 2001;894:255–65.

    CAS  PubMed  Google Scholar 

  42. van Kesteren RE, Carter C, Dissel HM, van Minnen J, Gouwenberg Y, Syed NI, et al. Local synthesis of actin-binding protein β-thymosin regulates neurite outgrowth. J Neurosci. 2006;26:152–7.

    Article  PubMed  Google Scholar 

  43. Fanni D, Gerosa C, Nemolato S, Locci A, Marinelli V, Cabras T. MUC1 in mesenchymal-to-epithelial transition during human nephrogenesis: changing the fate of renal progenitor/stem cells? J Matern Fetal Neonatal Med. 2011;2:63–6.

    Article  Google Scholar 

  44. Badamchian M, Damavandy AA, Goldstein AL. Development of an analytical HPLC methodology to study the effects of thymosin β4 on actin in sputum of cystic fibrosis patients. Ann N Y Acad Sci. 2012;1270:86–92.

    Article  CAS  PubMed  Google Scholar 

  45. Nemolato S, Cabras T, Fanari MU, Cau F, Fraschini M, Manconi B, et al. Thymosin beta 4 expression in normal skin, colon mucosa and in tumor infiltrating mast cells. Eur J Histochem. 2010;54:e3.

    CAS  PubMed Central  PubMed  Google Scholar 

  46. Larsson LI, Holck S. Occurrence of thymosin beta4 in human breast cancer cells and in other cell types of the tumor microenvironment. Hum Pathol. 2007;38:114–9.

    Article  CAS  PubMed  Google Scholar 

  47. Reti R, Kwon E, Qiu P, Wheater M, Sosne G. Thymosin beta4 is cytoprotective in human gingival fibroblasts. Eur J Oral Sci. 2008;116:424–30.

    Article  PubMed  Google Scholar 

  48. Sosne G, Szliter EA, Barrett R, Kernacki KA, Kleinman H, Hazlett LD. Thymosin beta 4 promotes corneal wound healing and decreases inflammation in vivo following alkali injury. Exp Eye Res. 2002;74:293–9.

    Article  CAS  PubMed  Google Scholar 

  49. Smart N, Rossdeutsch A, Riley PR. Thymosin beta4 and angiogenesis: modes of action and therapeutic potential. Angiogenesis. 2007;10:229–41.

    Article  CAS  PubMed  Google Scholar 

  50. Goldstein AL. Thymosin beta4: a new molecular target for antitumor strategies. J Natl Cancer Inst. 2003;95:1646–7.

    Article  CAS  PubMed  Google Scholar 

  51. Sun HQ, Kwiatkowska K, Yin HL. Beta-thymosins are not simple actin monomer buffering proteins. Insights from overexpression studies. J Biol Chem. 1996;271:9223–30.

    Article  CAS  PubMed  Google Scholar 

  52. Stossel TP, Fenteany G, Hartwig JH. Cell surface actin remodeling. J Cell Sci. 2006;119:3261–4.

    Article  CAS  PubMed  Google Scholar 

  53. Philp D, Goldstein AL, Kleinman HK. Thymosin beta4 promotes angiogenesis, wound healing, and hair follicle development. Mech Ageing Dev. 2004;125:113–5.

    Article  CAS  PubMed  Google Scholar 

  54. Bonnet D, Lemoine FM, Frobert Y, Bonnet ML, Baillou C, Najman A, et al. Thymosin beta4, inhibitor for normal hematopoietic progenitor cells. Exp Hematol. 1996;24:776–82.

    CAS  PubMed  Google Scholar 

  55. Moon HS, Even-Ram S, Kleinman HK, Cha HJ. Zyxin is upregulated in the nucleus by thymosin beta4 in SiHa cells. Exp Cell Res. 2006;312:3425–31.

    Article  CAS  PubMed  Google Scholar 

  56. Sun HQ, Yin HL. The beta-thymosin enigma. Ann N Y Acad Sci. 2007;1112:45–55.

    Article  CAS  PubMed  Google Scholar 

  57. Kupatt C, Horstkotte J, Vlastos GA, Pfosser A, Lebherz C, Semisch M, et al. Embryonic endothelial progenitor cells expressing a broad range of proangiogenic and remodeling factors enhance vascularization and tissue recovery in acute and chronic ischemia. FASEB J. 2005;19:1576–8.

    CAS  PubMed  Google Scholar 

  58. Nemolato S, Cabras T, Cau F, Fanari MU, Fanni D, Manconi B, et al. Different thymosin beta 4 immunoreactivity in foetal and adult gastrointestinal tract. PLoS One. 2010;5:e9111.

    Article  PubMed Central  PubMed  Google Scholar 

  59. Nemolato S, Van Eyken P, Cabras T, Cau F, Fanari MU, Locci A, et al. Expression pattern of thymosin beta 4 in the adult human liver. Eur J Histochem. 2011;55:e25.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Surgical Sciences, Division of Pathology, University of Cagliari, Cagliari, Italy

    Sonia Nemolato M.D. & Clara Gerosa M.D.

  2. Department of Life and Environmental Sciences, University of Cagliari, Cagliari, Italy

    Tiziana Cabras Ph.D. & Irene Messana Ph.D.

  3. Department of Surgical Sciences, Institute of Pathology, Azienda Ospedaliera Universitaria and University of Cagliari, Cagliari, Italy

    Gavino Faa M.D.

  4. Temple University, Philadelphia, PA, USA

    Gavino Faa M.D.

  5. Faculty of Medicine, Institute of Biochemistry and Clinical Biochemistry, Catholic University, Rome, Italy

    Massimo Castagnola Ph.D.

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  1. Sonia Nemolato M.D.
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  2. Tiziana Cabras Ph.D.
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  3. Irene Messana Ph.D.
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  4. Clara Gerosa M.D.
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  5. Gavino Faa M.D.
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  6. Massimo Castagnola Ph.D.
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Correspondence to Gavino Faa M.D. .

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Editors and Affiliations

  1. Department of Surgical Sciences, Division of Pathology, Azienda Ospedaliera Universitaria and University of Cagliari, Cagliari, Italy and Temple University, Philadelphia, Pennsylvania, USA

    Gavino Faa

  2. Neonatal Intensive Care Unit, Puericulture Institute and Neonatal Section, and Department of Surgery, Azienda Ospedaliera Universitaria Cagliari, Cagliari, Italy and University of Cagliari, Cagliari, Italy, Cagliari, Italy

    Vassilios Fanos

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Nemolato, S., Cabras, T., Messana, I., Gerosa, C., Faa, G., Castagnola, M. (2014). Do β-Thymosins Play a Role in Human Nephrogenesis?. In: Faa, G., Fanos, V. (eds) Kidney Development in Renal Pathology. Current Clinical Pathology. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-0947-6_8

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  • DOI: https://doi.org/10.1007/978-1-4939-0947-6_8

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