Table of Contents Author Guidelines Submit a Manuscript
International Journal of Cell Biology
Volume 2015 (2015), Article ID 563818, 8 pages
http://dx.doi.org/10.1155/2015/563818
Review Article

Size Matters: Molecular Weight Specificity of Hyaluronan Effects in Cell Biology

Laboratory of Respiratory Biology, Department of Intramural Research, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA

Received 7 October 2014; Accepted 5 January 2015

Academic Editor: Hans Hermann Gerdes

Copyright © 2015 Jaime M. Cyphert et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. J. Lesley, V. C. Hascall, M. Tammi, and R. Hyman, “Hyaluronan binding by cell surface CD44,” Journal of Biological Chemistry, vol. 275, no. 35, pp. 26967–26975, 2000. View at Publisher · View at Google Scholar · View at Scopus
  2. D. Jiang, J. Liang, and P. W. Noble, “Hyaluronan in tissue injury and repair,” Annual Review of Cell and Developmental Biology, vol. 23, pp. 435–461, 2007. View at Publisher · View at Google Scholar · View at Scopus
  3. T. C. Laurent and J. R. E. Fraser, “Hyaluronan,” The FASEB Journal, vol. 6, no. 7, pp. 2397–2404, 1992. View at Google Scholar · View at Scopus
  4. K. T. Dicker, L. A. Gurski, S. Pradhan-Bhatt, R. L. Witt, M. C. Farach-Carson, and X. Jia, “Hyaluronan: a simple polysaccharide with diverse biological functions,” Acta Biomaterialia, vol. 10, no. 4, pp. 1558–1570, 2014. View at Publisher · View at Google Scholar · View at Scopus
  5. A. P. Spicer and J. A. McDonald, “Characterization and molecular evolution of a vertebrate hyaluronan synthase gene family,” The Journal of Biological Chemistry, vol. 273, no. 4, pp. 1923–1932, 1998. View at Publisher · View at Google Scholar · View at Scopus
  6. P. Prehm, “Hyaluronate is synthesized at plasma membranes,” Biochemical Journal, vol. 220, no. 2, pp. 597–600, 1984. View at Google Scholar · View at Scopus
  7. P. Prehm, “Identification and regulation of the eukaryotic hyaluronate synthase,” Ciba Foundation Symposium, vol. 143, pp. 21–40, 1989. View at Google Scholar · View at Scopus
  8. N. Itano, T. Sawai, M. Yoshida et al., “Three isoforms of mammalian hyaluronan synthases have distinct enzymatic properties,” Journal of Biological Chemistry, vol. 274, no. 35, pp. 25085–25092, 1999. View at Publisher · View at Google Scholar · View at Scopus
  9. J. Y. L. Tien and A. P. Spicer, “Three vertebrate hyaluronan synthases are expressed during mouse development in distinct spatial and temporal patterns,” Developmental Dynamics, vol. 233, no. 1, pp. 130–141, 2005. View at Publisher · View at Google Scholar · View at Scopus
  10. T. D. Camenisch, A. P. Spicer, T. Brehm-Gibson et al., “Disruption of hyaluronan synthase-2 abrogates normal cardiac morphogenesis and hyaluronan-mediated transformation of epithelium to mesenchyme,” Journal of Clinical Investigation, vol. 106, no. 3, pp. 349–360, 2000. View at Publisher · View at Google Scholar · View at Scopus
  11. D. Jiang, J. Liang, and P. W. Noble, “Hyaluronan as an immune regulator in human diseases,” Physiological Reviews, vol. 91, no. 1, pp. 221–264, 2011. View at Publisher · View at Google Scholar · View at Scopus
  12. K. M. Stuhlmeier and C. Pollaschek, “Differential effect of transforming growth factor β (TGF-β) on the genes encoding hyaluronan synthases and utilization of the p38 MAPK pathway in TGF-β-induced hyaluronan synthase 1 activation,” Journal of Biological Chemistry, vol. 279, no. 10, pp. 8753–8760, 2004. View at Publisher · View at Google Scholar · View at Scopus
  13. S. Adamia, P. M. Pilarski, A. R. Belch, and L. M. Pilarski, “Aberrant splicing, hyaluronan synthases and intracellular hyaluronan as drivers of oncogenesis and potential drug targets,” Current Cancer Drug Targets, vol. 13, no. 4, pp. 347–361, 2013. View at Publisher · View at Google Scholar · View at Scopus
  14. Y. Li, D. Jiang, J. Liang et al., “Severe lung fibrosis requires an invasive fibroblast phenotype regulated by hyaluronan and CD44,” Journal of Experimental Medicine, vol. 208, no. 7, pp. 1459–1471, 2011. View at Publisher · View at Google Scholar · View at Scopus
  15. D. Jiang, J. Liang, J. Fan et al., “Regulation of lung injury and repair by Toll-like receptors and hyaluronan,” Nature Medicine, vol. 11, no. 11, pp. 1173–1179, 2005. View at Publisher · View at Google Scholar · View at Scopus
  16. A. B. Csoka, G. I. Frost, and R. Stern, “The six hyaluronidase-like genes in the human and mouse genomes,” Matrix Biology, vol. 20, no. 8, pp. 499–508, 2001. View at Publisher · View at Google Scholar · View at Scopus
  17. R. Stern and M. J. Jedrzejas, “Hyaluronidases: their genomics, structures, and mechanisms of action,” Chemical Reviews, vol. 106, no. 3, pp. 818–839, 2006. View at Publisher · View at Google Scholar · View at Scopus
  18. R. Stern, “Hyaluronan catabolism: a new metabolic pathway,” European Journal of Cell Biology, vol. 83, no. 7, pp. 317–325, 2004. View at Publisher · View at Google Scholar · View at Scopus
  19. K. Meyer, “Chemical structure of hyaluronic acid,” Federation Proceedings, vol. 17, no. 4, pp. 1075–1077, 1958. View at Google Scholar · View at Scopus
  20. M. Erickson and R. Stern, “Chain gangs: new aspects of hyaluronan metabolism,” Biochemistry Research International, vol. 2012, Article ID 893947, 9 pages, 2012. View at Publisher · View at Google Scholar · View at Scopus
  21. V. B. Lokeshwar and M. G. Selzer, “Hyalurondiase: both a tumor promoter and suppressor,” Seminars in Cancer Biology, vol. 18, no. 4, pp. 281–287, 2008. View at Publisher · View at Google Scholar · View at Scopus
  22. B. Triggs-Raine, T. J. Salo, H. Zhang, B. A. Wicklow, and M. R. Natowicz, “Mutations in HYAL1, a member of a tandemly distributed multigene family encoding disparate hyaluronidase activities, cause a newly described lysosomal disorder, mucopolysaccharidosis IX,” Proceedings of the National Academy of Sciences of the United States of America, vol. 96, no. 11, pp. 6296–6300, 1999. View at Publisher · View at Google Scholar · View at Scopus
  23. T. Kaneiwa, S. Mizumoto, K. Sugahara, and S. Yamada, “Identification of human hyaluronidase-4 as a novel chondroitin sulfate hydrolase that preferentially cleaves the galactosaminidic linkage in the trisulfated tetrasaccharide sequence,” Glycobiology, vol. 20, no. 3, pp. 300–309, 2009. View at Publisher · View at Google Scholar · View at Scopus
  24. L. Y. W. Bourguignon, P. A. Singleton, F. Diedrich, R. Stern, and E. Gilad, “CD44 interaction with Na+-H+ exchanger (NHE1) creates acidic microenvironments leading to hyaluronidase-2 and cathepsin B activation and breast tumor cell invasion,” Journal of Biological Chemistry, vol. 279, no. 26, pp. 26991–27007, 2004. View at Publisher · View at Google Scholar · View at Scopus
  25. M. R. Natowicz, M. P. Short, Y. Wang et al., “Clinical and biochemical manifestations of hyaluronidase deficiency,” The New England Journal of Medicine, vol. 335, no. 14, pp. 1029–1033, 1996. View at Publisher · View at Google Scholar · View at Scopus
  26. L. Jadin, X. Wu, H. Ding et al., “Skeletal and hematological anomalies in HYAL2-deficient mice: a second type of mucopolysaccharidosis IX?” The FASEB Journal, vol. 22, no. 12, pp. 4316–4326, 2008. View at Publisher · View at Google Scholar · View at Scopus
  27. B. Chowdhury, R. Hemming, S. Hombach-Klonisch, B. Flamion, and B. Triggs-Raine, “Murine hyaluronidase 2 deficiency results in extracellular hyaluronan accumulation and severe cardiopulmonary dysfunction,” The Journal of Biological Chemistry, vol. 288, no. 1, pp. 520–528, 2013. View at Publisher · View at Google Scholar · View at Scopus
  28. J. Muto, Y. Morioka, K. Yamasaki et al., “Hyaluronan digestion controls DC migration from the skin,” The Journal of Clinical Investigation, vol. 124, no. 3, pp. 1309–1319, 2014. View at Publisher · View at Google Scholar · View at Scopus
  29. R. Stern, G. Kogan, M. J. Jedrzejas, and L. Šoltés, “The many ways to cleave hyaluronan,” Biotechnology Advances, vol. 25, no. 6, pp. 537–557, 2007. View at Publisher · View at Google Scholar · View at Scopus
  30. M. Oettl, J. Hoechstetter, I. Asen, G. Bernhardt, and A. Buschauer, “Comparative characterization of bovine testicular hyaluronidase and a hyaluronate lyase from Streptococcus agalactiae in pharmaceutical preparations,” European Journal of Pharmaceutical Sciences, vol. 18, no. 3-4, pp. 267–277, 2003. View at Publisher · View at Google Scholar · View at Scopus
  31. L. Šoltés, R. Mendichi, G. Kogan, J. Schiller, M. Stankovská, and J. Arnhold, “Degradative action of reactive oxygen species on hyaluronan,” Biomacromolecules, vol. 7, no. 3, pp. 659–668, 2006. View at Publisher · View at Google Scholar · View at Scopus
  32. M. E. Monzon, N. Fregien, N. Schmid et al., “Reactive oxygen species and hyaluronidase 2 regulate airway epithelial hyaluronan fragmentation,” The Journal of Biological Chemistry, vol. 285, no. 34, pp. 26126–26134, 2010. View at Publisher · View at Google Scholar · View at Scopus
  33. F. Gao, J. R. Koenitzer, J. M. Tobolewski et al., “Extracellular superoxide dismutase inhibits inflammation by preventing oxidative fragmentation of hyaluronan,” Journal of Biological Chemistry, vol. 283, no. 10, pp. 6058–6066, 2008. View at Publisher · View at Google Scholar · View at Scopus
  34. G. M. Campo, A. Avenoso, A. D'Ascola et al., “Inhibition of hyaluronan synthesis reduced inflammatory response in mouse synovial fibroblasts subjected to collagen-induced arthritis,” Archives of Biochemistry and Biophysics, vol. 518, no. 1, pp. 42–52, 2012. View at Publisher · View at Google Scholar · View at Scopus
  35. G. M. Campo, A. Avenoso, A. D'Ascola et al., “The SOD mimic MnTM-2-PyP(5+) reduces hyaluronandegradation-induced inflammation in mouse articularchondrocytes stimulated with Fe (II) plus ascorbate,” International Journal of Biochemistry and Cell Biology, vol. 45, no. 8, pp. 1610–1619, 2013. View at Publisher · View at Google Scholar · View at Scopus
  36. I. Juranek, R. Stern, and L. Šoltes, “Hyaluronan peroxidation is required for normal synovial function: an hypothesis,” Medical Hypotheses, vol. 82, no. 6, pp. 662–666, 2014. View at Publisher · View at Google Scholar · View at Scopus
  37. D. Manzanares, M.-E. Monzon, R. C. Savani, and M. Salathe, “Apical oxidative hyaluronan degradation stimulates airway ciliary beating via RHAMM and RON,” The American Journal of Respiratory Cell and Molecular Biology, vol. 37, no. 2, pp. 160–168, 2007. View at Publisher · View at Google Scholar · View at Scopus
  38. S. M. Casalino-Matsuda, M. E. Monzon, G. E. Conner, M. Salathe, and R. M. Forteza, “Role of hyaluronan and reactive oxygen species in tissue kallikrein-mediated epidermal growth factor receptor activation in human airways,” Journal of Biological Chemistry, vol. 279, no. 20, pp. 21606–21616, 2004. View at Publisher · View at Google Scholar · View at Scopus
  39. K. S. Girish and K. Kemparaju, “The magic glue hyaluronan and its eraser hyaluronidase: a biological overview,” Life Sciences, vol. 80, no. 21, pp. 1921–1943, 2007. View at Publisher · View at Google Scholar · View at Scopus
  40. C. Hardwick, K. Hoare, R. Owens et al., “Molecular cloning of a novel hyaluronan receptor that mediates tumor cell motility,” The Journal of Cell Biology, vol. 117, no. 6, pp. 1343–1350, 1992. View at Publisher · View at Google Scholar · View at Scopus
  41. C. Termeer, F. Benedix, J. Sleeman et al., “Oligosaccharides of hyaluronan activate dendritic cells via Toll-like receptor 4,” Journal of Experimental Medicine, vol. 195, no. 1, pp. 99–111, 2002. View at Publisher · View at Google Scholar · View at Scopus
  42. R. M. Forteza, S. M. Casalino-Matsuda, N. S. Falcon, M. V. Gattas, and M. E. Monzon, “Hyaluronan and layilin mediate loss of airway epithelial barrier function induced by cigarette smoke by decreasing,” Journal of Biological Chemistry, vol. 287, no. 50, pp. 42288–42298, 2012. View at Publisher · View at Google Scholar · View at Scopus
  43. P. Bono, K. Rubin, J. M. G. Higgins, and R. O. Hynes, “Layilin, a novel integral membrane protein, is a hyaluronan receptor,” Molecular Biology of the Cell, vol. 12, no. 4, pp. 891–900, 2001. View at Publisher · View at Google Scholar · View at Scopus
  44. C. M. Carreira, S. M. Nasser, E. di Tomaso et al., “LYVE-1 is not restricted to the lymph vessels: expression in normal liver blood sinusoids and down-regulation in human liver cancer and cirrhosis,” Cancer Research, vol. 61, no. 22, pp. 8079–8084, 2001. View at Google Scholar · View at Scopus
  45. R. Prevo, S. Banerji, D. J. P. Ferguson, S. Clasper, and D. G. Jackson, “Mouse LYVE-1 is an endocytic receptor for hyaluronan in lymphatic endothelium,” Journal of Biological Chemistry, vol. 276, no. 22, pp. 19420–19430, 2001. View at Publisher · View at Google Scholar · View at Scopus
  46. S. Banerji, J. Ni, S.-X. Wang et al., “LYVE-1, a new homologue of the CD44 glycoprotein, is a lymph-specific receptor for hyaluronan,” The Journal of Cell Biology, vol. 144, no. 4, pp. 789–801, 1999. View at Publisher · View at Google Scholar · View at Scopus
  47. J. A. Weigel, R. C. Raymond, C. McGary, A. Singh, and P. H. Weigel, “A blocking antibody to the hyaluronan receptor for endocytosis (HARE) inhibits hyaluronan clearance by perfused liver,” Journal of Biological Chemistry, vol. 278, no. 11, pp. 9808–9812, 2003. View at Publisher · View at Google Scholar · View at Scopus
  48. J. A. Weigel, R. C. Raymond, and P. H. Weigel, “The hyaluronan receptor for endocytosis (HARE) is not CD44 or CD54 (ICAM-1),” Biochemical and Biophysical Research Communications, vol. 294, no. 4, pp. 918–922, 2002. View at Publisher · View at Google Scholar · View at Scopus
  49. B. Zhou, J. A. Weigel, L. Fauss, and P. H. Weigel, “Identification of the hyaluronan receptor for endocytosis (HARE),” Journal of Biological Chemistry, vol. 275, no. 48, pp. 37733–37741, 2000. View at Publisher · View at Google Scholar · View at Scopus
  50. B. P. Toole, S. Ghatak, and S. Misra, “Hyaluronan oligosaccharides as a potential anticancer therapeutic,” Current Pharmaceutical Biotechnology, vol. 9, no. 4, pp. 249–252, 2008. View at Publisher · View at Google Scholar · View at Scopus
  51. C. Yang, M. Cao, H. Liu et al., “The high and low molecular weight forms of hyaluronan have distinct effects on CD44 clustering,” The Journal of Biological Chemistry, vol. 287, no. 51, pp. 43094–43107, 2012. View at Publisher · View at Google Scholar · View at Scopus
  52. P. M. Wolny, S. Banerji, C. Gounou et al., “Analysis of CD44-hyaluronan interactions in an artificial membrane system: insights into the distinct binding properties of high and low molecular weight hyaluronan,” Journal of Biological Chemistry, vol. 285, no. 39, pp. 30170–30180, 2010. View at Publisher · View at Google Scholar · View at Scopus
  53. K. R. Taylor, K. Yamasaki, K. A. Radek et al., “Recognition of hyaluronan released in sterile injury involves a unique receptor complex dependent on toll-like receptor 4, CD44, and MD-2,” The Journal of Biological Chemistry, vol. 282, no. 25, pp. 18265–18275, 2007. View at Publisher · View at Google Scholar · View at Scopus
  54. S. Garantziotis, Z. Li, E. N. Potts et al., “Hyaluronan mediates ozone-induced airway hyperresponsiveness in mice,” The Journal of Biological Chemistry, vol. 284, no. 17, pp. 11309–11317, 2009. View at Publisher · View at Google Scholar · View at Scopus
  55. S. Garantziotis, Z. Li, E. N. Potts et al., “TLR4 is necessary for hyaluronan-mediated airway hyperresponsiveness after ozone inhalation,” The American Journal of Respiratory and Critical Care Medicine, vol. 181, no. 7, pp. 666–675, 2010. View at Publisher · View at Google Scholar · View at Scopus
  56. J. D. Powell and M. R. Horton, “Threat matrix: low-molecular-weight hyaluronan (HA) as a danger signal,” Immunologic Research, vol. 31, no. 3, pp. 207–218, 2005. View at Publisher · View at Google Scholar · View at Scopus
  57. G. M. Campo, A. Avenoso, S. Campo, A. D'Ascola, G. Nastasi, and A. Calatroni, “Small hyaluronan oligosaccharides induce inflammation by engaging both toll-like-4 and CD44 receptors in human chondrocytes,” Biochemical Pharmacology, vol. 80, no. 4, pp. 480–490, 2010. View at Publisher · View at Google Scholar · View at Scopus
  58. K. R. Taylor, J. M. Trowbridge, J. A. Rudisill, C. C. Termeer, J. C. Simon, and R. L. Gallo, “Hyaluronan fragments stimulate endothelial recognition of injury through TLR4,” The Journal of Biological Chemistry, vol. 279, no. 17, pp. 17079–17084, 2004. View at Publisher · View at Google Scholar · View at Scopus
  59. C. C. Termeer, J. Hennies, U. Voith et al., “Oligosaccharides of hyaluronan are potent activators of dendritic cells,” Journal of Immunology, vol. 165, no. 4, pp. 1863–1870, 2000. View at Publisher · View at Google Scholar · View at Scopus
  60. R. Schmits, J. Filmus, N. Gerwin et al., “CD44 regulates hematopoietic progenitor distribution, granuloma formation, and tumorigenicity,” Blood, vol. 90, no. 6, pp. 2217–2233, 1997. View at Google Scholar · View at Scopus
  61. V. A. Higman, D. C. Briggs, D. J. Mahoney et al., “A refined model for the TSG-6 link module in complex with hyaluronan: use of defined oligosaccharides to probe structure and function,” Journal of Biological Chemistry, vol. 289, no. 9, pp. 5619–5634, 2014. View at Publisher · View at Google Scholar · View at Scopus
  62. M. E. Lauer, T. T. Glant, K. Mikecz et al., “Irreversible heavy chain transfer to hyaluronan oligosaccharides by tumor necrosis factor-stimulated gene-6,” The Journal of Biological Chemistry, vol. 288, no. 1, pp. 205–214, 2013. View at Publisher · View at Google Scholar · View at Scopus
  63. K. A. Scheibner, M. A. Lutz, S. Boodoo, M. J. Fenton, J. D. Powell, and M. R. Horton, “Hyaluronan fragments act as an endogenous danger signal by engaging TLR2,” Journal of Immunology, vol. 177, no. 2, pp. 1272–1281, 2006. View at Publisher · View at Google Scholar · View at Scopus
  64. G. M. Campo, A. Avenoso, S. Campo, A. D'Ascola, P. Traina, and A. Calatroni, “Differential effect of molecular size HA in mouse chondrocytes stimulated with PMA,” Biochimica et Biophysica Acta—General Subjects, vol. 1790, no. 10, pp. 1353–1367, 2009. View at Publisher · View at Google Scholar · View at Scopus
  65. G. M. Campo, A. Avenoso, A. D'Ascola et al., “Hyaluronan differently modulates TLR-4 and the inflammatory response in mouse chondrocytes,” BioFactors, vol. 38, no. 1, pp. 69–76, 2012. View at Publisher · View at Google Scholar · View at Scopus
  66. G. M. Campo, A. Avenoso, A. D'Ascola et al., “4-mer hyaluronan oligosaccharides stimulate inflammation response in synovial fibroblasts in part via TAK-1 and in part via p38-MAPK,” Current Medicinal Chemistry, vol. 20, no. 9, pp. 1162–1172, 2013. View at Publisher · View at Google Scholar · View at Scopus
  67. F. Gao, C. X. Yang, W. Mo, Y. W. Liu, and Y. Q. He, “Hyaluronan oligosaccharides are potential stimulators to angiogenesis via RHAMM mediated signal pathway in wound healing,” Clinical and Investigative Medicine, vol. 31, no. 3, pp. E106–E116, 2008. View at Google Scholar · View at Scopus
  68. S. P. Evanko, T. Parks, and T. N. Wight, “Intracellular hyaluronan in arterial smooth muscle cells: association with microtubules, RHAMM, and the mitotic spindle,” Journal of Histochemistry and Cytochemistry, vol. 52, no. 12, pp. 1525–1535, 2004. View at Publisher · View at Google Scholar · View at Scopus
  69. S. P. Evanko and T. N. Wight, “Intracellular localization of hyaluronan in proliferating cells,” Journal of Histochemistry and Cytochemistry, vol. 47, no. 10, pp. 1331–1342, 1999. View at Publisher · View at Google Scholar · View at Scopus
  70. S. Adamia, J. Kriangkum, A. R. Belch, and L. M. Pilarski, “Aberrant posttranscriptional processing of hyaluronan synthase 1 in malignant transformation and tumor progression,” in Advances in Cancer Research, vol. 123, pp. 67–94, Elsevier, New York, NY, USA, 2014. View at Publisher · View at Google Scholar
  71. V. C. Hascall, A. K. Majors, C. A. de la Motte et al., “Intracellular hyaluronan: a new frontier for inflammation?” Biochimica et Biophysica Acta, vol. 1673, no. 1-2, pp. 3–12, 2004. View at Publisher · View at Google Scholar · View at Scopus
  72. R. Stern, “Hyaluronidases in cancer biology,” Seminars in Cancer Biology, vol. 18, no. 4, pp. 275–280, 2008. View at Publisher · View at Google Scholar · View at Scopus
  73. G. M. Campo, A. Avenoso, A. D'Ascola et al., “The inhibition of hyaluronan degradation reduced pro-inflammatory cytokines in mouse synovial fibroblasts subjected to collagen-induced arthritis,” Journal of Cellular Biochemistry, vol. 113, no. 6, pp. 1852–1867, 2012. View at Publisher · View at Google Scholar · View at Scopus
  74. E. N. Harris, S. V. Kyosseva, J. A. Weigel, and P. H. Weigel, “Expression, processing, and glycosaminoglycan binding activity of the recombinant human 315-kDa hyaluronic acid receptor for endocytosis (HARE),” The Journal of Biological Chemistry, vol. 282, no. 5, pp. 2785–2797, 2007. View at Publisher · View at Google Scholar · View at Scopus
  75. Q. Hua, C. B. Knudson, and W. Knudson, “Internalization of hyaluronan by chondrocytes occurs via receptor-mediated endocytosis,” Journal of Cell Science, vol. 106, part 1, pp. 365–375, 1993. View at Google Scholar · View at Scopus
  76. H. J. Greyner, T. Wiraszka, L.-S. Zhang, W. M. Petroll, and M. E. Mummert, “Inducible macropinocytosis of hyaluronan in B16-F10 melanoma cells,” Matrix Biology, vol. 29, no. 6, pp. 503–510, 2010. View at Publisher · View at Google Scholar · View at Scopus
  77. L. Rodén, P. Campbell, J. R. Fraser, T. C. Laurent, H. Pertoft, and J. N. Thompson, “Enzymic pathways of hyaluronan catabolism.,” Ciba Foundation symposium, vol. 143, pp. 60–76, 1989. View at Google Scholar · View at Scopus
  78. L. Gushulak, R. Hemming, D. Martin, V. Seyrantepe, A. Pshezhetsky, and B. Triggs-Raine, “Hyaluronidase 1 and β-hexosaminidase have redundant functions in hyaluronan and chondroitin sulfate degradation,” The Journal of Biological Chemistry, vol. 287, no. 20, pp. 16689–16697, 2012. View at Publisher · View at Google Scholar · View at Scopus
  79. Y.-Y. Liu, C.-H. Lee, R. Dedaj et al., “High-molecular-weight hyaluronan—a possible new treatment for sepsis-induced lung injury: a preclinical study in mechanically ventilated rats,” Critical Care, vol. 12, no. 4, article R102, 2008. View at Publisher · View at Google Scholar · View at Scopus
  80. Z. Li, E. N. Potts-Kant, S. Garantziotis, W. M. Foster, and J. W. Hollingsworth, “Hyaluronan signaling during ozone-induced lung injury requires TLR4, MyD88, and TIRAP,” PLoS ONE, vol. 6, no. 11, Article ID e27137, 2011. View at Publisher · View at Google Scholar · View at Scopus
  81. F. Feng, Z. Li, E. N. Potts-Kant et al., “Hyaluronan activation of the Nlrp3 inflammasome contributes to the development of airway hyperresponsiveness,” Environmental Health Perspectives, vol. 120, no. 12, pp. 1692–1698, 2012. View at Publisher · View at Google Scholar · View at Scopus
  82. A. Varricchio, M. Capasso, F. Avvisati et al., “Inhaled hyaluronic acid as ancillary treatment in children with bacterial acute rhinopharyngitis,” Journal of Biological Regulators and Homeostatic Agents, vol. 28, no. 3, pp. 537–43, 2014. View at Google Scholar
  83. M. Ros, R. Casciaro, F. Lucca et al., “Hyaluronic acid improves the tolerability of hypertonic saline in the chronic treatment of cystic fibrosis patients: a multicenter, randomized, controlled clinical trial,” Journal of Aerosol Medicine and Pulmonary Drug Delivery, vol. 27, no. 2, pp. 133–137, 2014. View at Publisher · View at Google Scholar · View at Scopus
  84. F. Cresta, A. Naselli, F. Favilli, and R. Casciaro, “Inhaled hypertonic saline+hyaluronic acid in cystic fibrosis with asthma-like symptoms: a new therapeutic chance,” BMJ Case Reports, vol. 2013, 2013. View at Publisher · View at Google Scholar
  85. M. L. Furnari, L. Termini, G. Traverso et al., “Nebulized hypertonic saline containing hyaluronic acid improves tolerability in patients with cystic fibrosis and lung disease compared with nebulized hypertonic saline alone: a prospective, randomized, double-blind, controlled study,” Therapeutic Advances in Respiratory Disease, vol. 6, no. 6, pp. 315–322, 2012. View at Publisher · View at Google Scholar · View at Scopus
  86. M. R. Horton, C. M. McKee, C. Bao et al., “Hyaluronan fragments synergize with interferon-γ to induce the C-X-C chemokines mig and interferon-inducible protein-10 in mouse macrophages,” The Journal of Biological Chemistry, vol. 273, no. 52, pp. 35088–35094, 1998. View at Publisher · View at Google Scholar · View at Scopus
  87. F. E. Lennon and P. A. Singleton, “Role of hyaluronan and hyaluronan-binding proteins in lung pathobiology,” The American Journal of Physiology—Lung Cellular and Molecular Physiology, vol. 301, no. 2, pp. L137–L147, 2011. View at Publisher · View at Google Scholar · View at Scopus
  88. A. R. Poole, J. Witter, N. Roberts et al., “Inflammation and cartilage metabolism in rheumatoid arthritis: studies of the blood markers hyaluronic acid, orosomucoid, and keratan sulfate,” Arthritis and Rheumatism, vol. 33, no. 6, pp. 790–799, 1990. View at Publisher · View at Google Scholar · View at Scopus
  89. B. P. Toole, A. Zoltan-Jones, S. Misra, and S. Ghatak, “Hyaluronan: a critical component of epithelial-mesenchymal and epithelial-carcinoma transitions,” Cells Tissues Organs, vol. 179, no. 1-2, pp. 66–72, 2005. View at Publisher · View at Google Scholar · View at Scopus
  90. M. Y. Kim, J. Muto, and R. L. Gallo, “Hyaluronic acid oligosaccharides suppress TLR3-dependent cytokine expression in a TLR4-dependent manner,” PLoS ONE, vol. 8, no. 8, Article ID e72421, 2013. View at Publisher · View at Google Scholar · View at Scopus
  91. C. W. Winkler, S. C. Foster, A. Itakura et al., “Hyaluronan oligosaccharides perturb lymphocyte slow rolling on brain vascular endothelial cells: implications for inflammatory demyelinating disease,” Matrix Biology, vol. 32, no. 3-4, pp. 160–168, 2013. View at Publisher · View at Google Scholar · View at Scopus
  92. S. Ghatak, S. Misra, and B. P. Toole, “Hyaluronan constitutively regulates ErbB2 phosphorylation and signaling complex formation in carcinoma cells,” The Journal of Biological Chemistry, vol. 280, no. 10, pp. 8875–8883, 2005. View at Publisher · View at Google Scholar · View at Scopus
  93. S. Misra, B. P. Toole, and S. Ghatak, “Hyaluronan constitutively regulates activation of multiple receptor tyrosine kinases in epithelial and carcinoma cells,” The Journal of Biological Chemistry, vol. 281, no. 46, pp. 34936–34941, 2006. View at Publisher · View at Google Scholar · View at Scopus