Expressions of TGF-β1 and MMP-9 in a guinea pig model of tympanosclerosis: Possible role in the pathogenesis of this disorder

Authors

  • Wentao Guo MD,

    1. Department of Otorhinolaryngology Head and Neck Surgery, Provincial Hospital affiliated to Shandong University, Jinan
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    • Wentao Guo, MD, and Xiaohui Bai, PhD, contributed equally to this work.

  • Xiaohui Bai PhD,

    1. Department of Otorhinolaryngology Head and Neck Surgery, Provincial Hospital affiliated to Shandong University, Jinan
    2. The Shandong Provincial Key Laboratory of Otology, Jinan
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    • Wentao Guo, MD, and Xiaohui Bai, PhD, contributed equally to this work.

  • Yuechen Han PhD,

    1. Department of Otorhinolaryngology Head and Neck Surgery, Provincial Hospital affiliated to Shandong University, Jinan
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  • Lei Xu PhD,

    1. Department of Otorhinolaryngology Head and Neck Surgery, Provincial Hospital affiliated to Shandong University, Jinan
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  • Wenwen Liu MD,

    1. Department of Otorhinolaryngology Head and Neck Surgery, Provincial Hospital affiliated to Shandong University, Jinan
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  • Guodong Zhang MD,

    1. Department of Otorhinolaryngology Head and Neck Surgery, Provincial Hospital affiliated to Shandong University, Jinan
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  • Jianfeng Li PhD,

    1. Department of Otorhinolaryngology Head and Neck Surgery, Provincial Hospital affiliated to Shandong University, Jinan
    2. The Shandong Provincial Key Laboratory of Otology, Jinan
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  • Zhaomin Fan MD,

    Corresponding author
    1. Department of Otorhinolaryngology Head and Neck Surgery, Provincial Hospital affiliated to Shandong University, Jinan
    • Department of Otorhinolaryngology–Head and Neck Surgery, Provincial Hospital affiliated to Shandong University, Jinan 250021, P.R. China
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  • Haibo Wang MD

    Corresponding author
    1. Department of Otorhinolaryngology Head and Neck Surgery, Provincial Hospital affiliated to Shandong University, Jinan
    2. The Shandong Provincial Key Laboratory of Otology, Jinan
    3. Institute of Eye and ENT, Provincial Hospital affiliated to Shandong University, Jinan, China
    • Department of Otorhinolaryngology–Head and Neck Surgery, Provincial Hospital affiliated to Shandong University, Jinan 250021, P.R. China
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  • This work was supported by the National Natural Science Foundation of China (81000407, 30870121), the Shandong Provincial Outstanding Young Scientist Research Award Fund (BS2010YY051), and Department of Science and Technology of Shandong Province (2006GG2202).

  • The authors have no other funding, financial relationships, or conflicts of interest to disclose.

Abstract

Objectives/Hypothesis:

The present study was performed to investigate the expressions of transforming growth factor β1 (TGF-β1) and matrix metalloproteinase-9 (MMP-9) in an experimental model of tympanosclerosis and their possible roles in the formation of this disorder.

Study Design:

A prospective experimental animal study.

Methods:

Seventy guinea pigs were used in this study, of which 10 were chosen to serve as controls, and the other 60 were used in the tympanosclerosis group by inoculation of type-3 Streptococcus pneumoniae microorganisms. The experimental animals were further divided into six subgroups on the basis of six time points. Otomicroscopy was employed to observe the development of myringosclerosis. Hematoxylin-eosin and von Kossa staining were performed to determine the morphological changes and calcium depositions. The expressions of TGF-β1 and MMP-9 were assessed by Western blot and immunohistochemistry.

Results:

Slight sclerotic changes in tympanic membrane were found at week 2, and extensive myringosclerosis was observed at week 6. Hyalinization and calcification in the tympanic membrane and middle ear mucous membrane were clearly visible at week 6. Expression of TGF-β1 was significantly increased with the development of tympanosclerosis. Expression of MMP-9 was increased from week 1 to week 4, and then declined at week 6. These two cytokines were both distributed in the cytoplasm of fibroblast cells and inflammatory cells, which were widely distributed in the tympanic membrane and middle ear mucosa at week 6.

Conclusions:

Our data indicate that, for the first time, the alteration in expressions of TGF-β1 and MMP-9 were involved in the formation of tympanosclerosis, which may represent an important mechanism underlying the pathogenesis of tympanosclerosis. Laryngoscope, 2012

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