Advances in Clinical and Experimental Medicine

Title abbreviation: Adv Clin Exp Med
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Advances in Clinical and Experimental Medicine

2017, vol. 26, nr 6, September, p. 961–966

doi: 10.17219/acem/68984

Publication type: original article

Language: English

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Gene expression profile of collagen types, osteopontin in the tympanic membrane of patients with tympanosclerosis

Monika Sakowicz-Burkiewicz1,A,C,D,E,F, Jerzy Kuczkowski2,B,E, Tomasz Przybyła1,B,C,E, Marzena Grdeń1,C,E, Anna Starzyńska3,B,E, Tadeusz Pawełczyk1,A,E,F

1 Department of Molecular Medicine, Medical University of Gdańsk, Poland

2 Department of Otolaryngology, Medical University of Gdańsk, Poland

3 Department of Orofacial and Dental Surgery, Medical University of Gdańsk, Poland

Abstract

Background. Tympanosclerosis is a pathological process involving the middle ear. The hallmark of this disease is the formation of calcium deposits. In the submucosal layer, as well as in the right layer of the tympanic membrane, the calcium deposits result in a significant increase in the activity of fibroblasts and deposition of collagen fibers.
Objectives. The aim of our study was to examine the expression level of genes encoding collagen type I, II, III and IV (COL1A1, COL2A1, COL3A1, COL4A1) and osteopontin (SPP1) in the tympanic membrane of patients with tympanosclerosis.
Material and Methods. The total RNA was isolated from middle ear tissues with tympanosclerosis, received from 25 patients and from 19 normal tympanic membranes. The gene expression level was determined by real-time RT-PCR. The gene expression levels were correlated with clinical Tos classification of tympanosclerosis.
Results. We observed that in the tympanic membrane of patients with tympanosclerosis, the expression of type I collagen is decreased, while the expression of type II and IV collagen and osteopontin is increased. Moreover, mRNA levels of the investigated genes strongly correlated with the clinical stages of tympanosclerosis.
Conclusion. The strong correlations between the expression of type I, II, IV collagen and osteopontin and the clinical stage of tympanosclerosis indicate the involvement of these proteins in excessive fibrosis and pathological remodeling of the tympanic membrane. In the future, a treatment aiming to modulate these gene expressions and/or regulation of the degradation of their protein products could be used as a new medical approach for patients with tympanosclerosis.

Key words

osteopontin, tympanosclerosis, collagen types

References (40)

  1. Asiri S, Hasham A, al Anazy F, Zakzouk S, Banjar A. Tympanosclerosis: review of literature and incidence among patients with middle-ear infection. J Laryngol Otol. 1999;113:1076–80.
  2. Sheehy JL, House WF. Tympanosclerosis. Arch Otolaryngol. 1962;76:151–157.
  3. Horowitz S. Heterotopic ossification in the middle ear. J Laryng Otol. 1952;66:181–186.
  4. Tukaj C, Kuczkowski J, Sakowicz-Burkiewicz M, et al. Morphological alterations in the tympanic membrane affected by tympanosclerosis: Ultrastructural study. Ultrastruct Pathol. 2014;38:69–73.
  5. Skarżyński H. Zalecany standard postępowania w operacjach poprawiających słuch w tympanosklerozie (stadium literaturowe, doświadczenia praktyczne). http://ifps.org.pl/doc/material_dydaktyka/skarzynski4.pdf. (read on 9 Nov. 2015)
  6. Harris I. Tympanosclerosis – a revived clinicopathologic entity. The Laryngoscope. 1961;71:1488–1533.
  7. da Costa SS, Paparella MM, Schachern PA, Yoon TH, Kimberley BP. Temporal bone histopathology in chronically infected ears with intact and perforated tympanic membranes. Laryngoscope. 1992;102:1229–1236.
  8. Chang I. Tympanosclerosis. Acta Otolaryngol. 1969;68:62–72.
  9. Gibb AG, Pang YT. Current considerations in the etiology and diagnosis of tympanosclerosis. Eur Arch Otorhinolaryngol. 1994;251:439–451.
  10. Tos M, Stangerup SE, Larsen P. Dynamics of eardrum changes following secretory otitis: A prospective study. Arch Otolaryngol Head Neck Surg. 1987;113:380–385.
  11. Hassmann-Poznańska E, Goździewski A, Piszcz M, Skotnicka B. Long term sequelae of otitis media with effusion during childhood. Otolaryngol Pol. 2010;64:234–239.
  12. Zielnik-Jurkiewicz B, Olszewska-Sosińska O, Rakowska M. Results of treatment with tympanostomy tubes in children with otitis media with effusion. Otolaryngol Pol. 2006;60:181–185.
  13. Forséni M, Bagger-Sjöbäck D, Hultcrantz M. A study of inflammatory mediators in the human tympanosclerotic middle ear. Arch Otolaryngol Head Neck Surg. 2001;127:559–564.
  14. Schiff M, Yoo TJ. Immunologic aspects of otologic disease: An overview. Laryngoscope. 1985;95:259–269.
  15. Koc A, Uneri C. Genetic predisposition for tympansclerotic degeneration. Eur Arch Otorhinolaryngol. 2002;259:180–183.
  16. de Carvalho Leal M, Ferreira Bento R, da Silva Caldas Neto S, et al. Influence of hypercalcemia in the formation of tympanosclerosis in rats. Otol Neurotol. 2006;27:27–32.
  17. Tos M. Surgical solutions for conductive hearing loss. Stuttgart, New York: Thieme; 2000.
  18. Pawelczyk T, Sakowicz-Burkiewicz M, Wesserling M, Grden M, Kuczkowski J. Altered response of fibroblasts from human tympanosclerotic membrane to interacting mast cells: Implication for tissue remodeling. Int J Biochem Cell Biol. 2014;57:35–44.
  19. Mionskowski T, Kuczkowski J, Sakowicz-Burkiewicz M. Określenie profilu ekspresji genu TNFα w wybranych strukturach ucha środkowego u chorych na tympanosklerozę. Otolaryngol Pol. 2012;66:20–24.
  20. Chomczynski P, Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem. 1987;162:156–159.
  21. Huang ZY, Zhou FH, Xie NP, Guo MH, Wan LC, Sun WQ. Clinical analysis of 11 patients with tympanosclerosis. Nan Fang Yi Ke Da Xue Xue Bao. 2010;30:345–348.
  22. Kinney SE. Postinflammatory ossicular fixation in tympanoplasty. Laryngoscope. 1978;88:821–38.
  23. Vlastarakos PV, Nikolopoulos TP, Korres S, Tavoulari E, Tzagaroulakis A, Ferekidis E. Grommets in otitis media with effusion: The most frequent operation in children. But is it associated with significant complications? Eur J Pediatr. 2007;166:385–391.
  24. Slack RW, Maw AR, Capper JW, Kelly S. Prospective study of tympanosclerosis developing after grommet insertion. J Laryngol Otol. 1984;98:771–774.
  25. Yaman H, Yilmaz S, Alkan N, Subasi B, Guclu E, Ozturk O. Shepard grommet tympanostomy tube complications in children with chronic otitis media with effusion. Eur Arch Otorhinolaryngol. 2010;267:1221–1224.
  26. Kay DJ, Nelson M, Rosenfeld RM. Meta-analysis of tympanostomy tube sequelae. Otolaryngol Head Neck Surg. 2001;124:374–80.
  27. Cayé-Thomasen P, Stangerup SE, Jorgensen G, Drozdziewic D,Bonding P, Tos M. Myringotomy versus ventilation tubes in secretory otitis media: Eardrum pathology, hearing, and eustachian tube function 25 years after treatment. Otol Neurotol. 2008;29:649–657.
  28. Pereira MB, Pereira DR, Costa SS. Tympanostomy tube sequelae in children with otitis media with effusion: A three-year follow-up study. Braz J Otorhinolaryngol. 2005;71:415–420.
  29. Yaman H, Guclu E, Yilmaz S, Ozturk O. Myringosclerosis after tympanostomy tube insertion: Relation with tube retention time and gender. Auris Nasus Larynx. 2010;37:676–679.
  30. Tos M, Stangerup SE. Hearing loss in tympanosclerosis caused by grommets. Arch Otolaryngol Head Neck Surg. 1989;115:931–935.
  31. Maw AR. Development of tympanosclerosis in children with otitis media with effusion and ventilation tubes. J Laryngol Otol. 1991;105:614–761.
  32. Yaman H, Yilmaz S, Guclu E, Subasi B, Alkan N, Ozturk O. Otitis media with effusion: Recurrence after tympanostomy tube extrusion. Int J Pediatr Otorhinolaryngol. 2010;74:271–274.
  33. Lesser TH, Williams KR, Skinner DW. Tympanosclerosis, grommets and shear stresses. Clin Otolaryngol Allied Sci. 1988;13:375–380.
  34. Koc A, Uneri C. Sex distribution in children with tympanosclerosis after insertion of a tympanostomy tube. Eur Arch Otorhinolaryngol. 2001;258:16–19.
  35. Knutsson J, Bagger-Sjöbäck D, von Unge M. Collagen type distribution in healthy human tympanic membrane. Otol Neurotol. 2009;30:1225–1229.
  36. Gelse K, Pöschl E, Aigner T. Collagens-structure, function, and biosynthesis. Adv Drug Deliv Rev. 2003;55:1531–1546.
  37. Yoo TJ, Sudo N, Tomoda K, et al. Type II collagen mediated autoimmune middle ear disease: Eustachian tube disease, otitis media with effusion and tympanosclerosis. Auris Nasus Larynx. 1985;12:S91–S93.
  38. Yoo TJ, Floyd RA, Sudo N, et al. Factors influencing collagen-induced autoimmune ear disease. Am J Otolaryngol. 1985;6:209–216.
  39. Cho HJ, Cho HJ, Kim HS. Osteopontin: A multifunctional protein at the crossroads of inflammation, atherosclerosis, and vascular calcification. Curr Atheroscler Rep. 2009;11:206–213.
  40. Makiishi-Shimobayashi C, Tsujimura T, Sugihara A, et al. Expression of osteopontin by exudate macrophages in inflammatorytissues of the middle ear: A possible association with development of tympanosclerosis. Hearing Res. 2001:153:100–107.
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