Age-dependent changes in the expression of klotho protein, TRPV5 and TRPV6 in mouse inner ear.
CONCLUSIONS
Klotho protein content decreases with increasing age, which weakens resistance to oxidative stress, resulting in induced cell death as well as modulating endolymph fluid homeostasis. Down-regulation of klotho also leads to down-regulation of TRPV5 and TRPV6, resulting in modified Ca(2+) homeostasis in the inner ear, dysfunction of sensory cell transduction and causing hearing loss and/or vestibular disorders.


OBJECTIVE
Expression of klotho, TRPV5 and TRPV6 in the mouse inner ear and age-related changes were analysed.


METHODS
CBA/J mice aged 8 weeks and 24 months were used in this study. The localization of klotho, TRPV5 and TRPV6 in the inner ear of young and old mice was investigated by immunohistochemistry.


RESULTS
Immunostaining for klotho was observed in stria vascularis, outer and inner hair cells (OHCs and IHCs), and in vestibular sensory cells and dark cells, and less intensely in the spiral and vestibular ganglion cells. Expression of TRPV5 was found in stria vascularis, organ of Corti, vestibular sensory cells and dark cells, and less intensely in the spiral and vestibular ganglion cells. Expression of TRPV6 was found in supporting cells of the organ of Corti, with weak labelling in OHCs and IHCs. Weak fluorescence was also noted in stria vascularis, and faint fluorescence in the spiral ligament. Vestibular sensory and dark cells as well as vestibular ganglion cells showed weak fluorescence. In the old animals, the expression patterns of klotho, TRPV5 and TRPV6 were identical with those in young animals, although fluorescence intensity was significantly weaker.
Takumida
Masaya
M
Department of Otolaryngology, Hiroshima University Faculty of Medicine, Hiroshima, Japan. masati@hiroshima-u.ac.jp
Ishibashi
Takuya
T
Hamamoto
Takao
T
Hirakawa
Katsuhiro
K
Anniko
Matti
M
D000375:Aging / Q000502:physiology*; D000447:Aldehydes / Q000378:metabolism; D000818:Animals; D015220:Calcium Channels / Q000378:metabolism*; D007758:Ear, Inner / Q000378:metabolism*; D005966:Glucuronidase / Q000378:metabolism*; D000090265:Klotho Proteins; D051379:Mice; D008808:Mice, Inbred CBA; D008853:Microscopy; D013482:Superoxide Dismutase / Q000378:metabolism; D050916:TRPV Cation Channels / Q000378:metabolism*; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism; D000099156:Superoxide Dismutase 2
D000447:Aldehydes; D015220:Calcium Channels; D005966:Glucuronidase; D000090265:Klotho Proteins; D013482:Superoxide Dismutase; D050916:TRPV Cation Channels; D014443:Tyrosine; D000099156:Superoxide Dismutase 2; C492240:Trpv5 protein, mouse; C446923:Trpv6 protein, mouse; C002744:3-nitrotyrosine; C027576:4-hydroxy-2-nonenal