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Hepatocyte growth factor protects auditory hair cells from aminoglycosides
Author(s) -
Kikkawa Yayoi S.,
Nakagawa Takayuki,
Tsubouchi Hirohito,
Ido Akio,
Inaoka Takatoshi,
Ono Kazuya,
Ito Juichi
Publication year - 2009
Publication title -
the laryngoscope
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.181
H-Index - 148
eISSN - 1531-4995
pISSN - 0023-852X
DOI - 10.1002/lary.20602
Subject(s) - hepatocyte growth factor , neomycin , cochlea , ototoxicity , hair cell , immunostaining , immunohistochemistry , organ of corti , lipid peroxidation , blot , microbiology and biotechnology , inner ear , western blot , biology , chemistry , medicine , endocrinology , immunology , anatomy , receptor , biochemistry , oxidative stress , cisplatin , antibiotics , chemotherapy , gene
Objectives/Hypothesis: To examine the effect of hepatocyte growth factor (HGF) for protection of auditory hair cells against aminoglycosides and its molecular mechanisms. Study Design: Experimental study. Methods: We quantitatively assessed protective effects of HGF on mouse cochlear hair cells against neomycin toxicity using explant culture systems. To understand mechanisms of hair cell protection by HGF, we examined the expression of c‐Met, HGF receptor, and 4‐hydroxynonenal (a lipid peroxidation marker) in the cochlea by means of immunohistochemistry and Western blotting. Results: The application of HGF to cochlear explant cultures significantly reduced the hair cell loss induced by neomycin. Immunohistochemistry showed c‐Met expression in normal auditory hair cells, and its increase in response to neomycin‐induced damage. Immunostaining for 4‐hydroxynonenal suggested that HGF acted by attenuating the lipid peroxidation of auditory epithelia induced by neomycin. Conclusions: These findings demonstrate that a functional HGF/c‐Met coupling is present in the cochlea, and HGF application exerts protective effects on hair cells, indicating the potential of HGF as a therapeutic agent for sensorineural hearing loss. Laryngoscope, 2009