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

• Published in: The Laryngoscope 2012-09, Vol.122 (9), p.2037-2042
• Main Authors: Guo, Wentao, Bai, Xiaohui, Han, Yuechen, Xu, Lei, Liu, Wenwen, Zhang, Guodong, Li, Jianfeng, Fan, Zhaomin, Wang, Haibo
• Format: Article
• Language: English
• Subjects: Analysis of Variance; Animals; Biological and medical sciences; Biomarkers - metabolism; Biopsy, Needle; Blotting, Western; Disease Models, Animal; Ear, auditive nerve, cochleovestibular tract, facial nerve: diseases, semeiology; Gene Expression Regulation; Guinea Pigs; Immunohistochemistry; Male; Matrix Metalloproteinase 9 - genetics; Matrix Metalloproteinase 9 - metabolism; mechanism; Medical sciences; MMP-9; Non tumoral diseases; Otorhinolaryngology. Stomatology; pathogenesis; Random Allocation; Sclerosis - metabolism; Sclerosis - pathology; Sclerosis - physiopathology; TGF-β1; Transforming Growth Factor beta - genetics; Transforming Growth Factor beta - metabolism; Tympanic Membrane - metabolism; Tympanic Membrane - pathology; Tympanic Membrane - physiopathology; Tympanosclerosis
• ISSN: 0023-852X; 1531-4995
• DOI: 10.1002/lary.23415

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