Hepatocyte growth factor protects auditory hair cells from aminoglycosides.
OBJECTIVE
To examine the effect of hepatocyte growth factor (HGF) for protection of auditory hair cells against aminoglycosides and its molecular mechanisms.


METHODS
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.
Kikkawa
Yayoi S
YS
Department of Otolaryngology-Head and Neck Surgery, Graduate School of Medicine, Kyoto University, Kawaharacho 54, Shogoin, Sakyo-ku, Kyoto, Japan.
Nakagawa
Takayuki
T
Tsubouchi
Hirohito
H
Ido
Akio
A
Inaoka
Takatoshi
T
Ono
Kazuya
K
Ito
Juichi
J
D000818:Animals; D006198:Hair Cells, Auditory / Q000187:drug effects* / Q000378:metabolism; D006319:Hearing Loss, Sensorineural / Q000188:drug therapy; D017228:Hepatocyte Growth Factor / Q000378:metabolism / Q000494:pharmacology*; D007150:Immunohistochemistry; D015227:Lipid Peroxidation / Q000187:drug effects; D051379:Mice; D008813:Mice, Inbred ICR; D009355:Neomycin / Q000009:adverse effects*; D018384:Oxidative Stress / Q000187:drug effects; D011500:Protein Synthesis Inhibitors / Q000009:adverse effects*; D019859:Proto-Oncogene Proteins c-met / Q000378:metabolism
D011500:Protein Synthesis Inhibitors; D017228:Hepatocyte Growth Factor; D019859:Proto-Oncogene Proteins c-met; D009355:Neomycin