Insulin-like growth factor 1: A novel treatment for the protection or regeneration of cochlear hair cells.
Sensorineural hearing loss (SNHL) is mainly caused by cochlear hair cell damage. Because cochlear hair cells and supporting cells lose their ability to proliferate in postnatal mammals, SNHL was thought to be an intractable disease. The maintenance of hair cell and supporting cell numbers after cochlear injury is therefore important for the treatment of sensorineural hearing loss. To achieve such treatment, protection and/or regeneration of hair cells is necessary. Progress in cochlear injury research, developmental biology, and regenerative medicine has led to the discovery of cochlear hair cells being protected or regenerated not only by direct reaction of hair cells themselves but also by that of supporting cells. Insulin-like growth factor 1 (IGF1) is considered a novel and potent treatment for SNHL based on the findings of various in vivo and in vitro experiments and clinical trials. The application of IGF1 maintains hair cell number of postnatal mammalian cochleae after various kinds of ototoxicity including aminoglycoside treatment, noise exposure, and ischemia. The positive effects of IGF1 on hair cell damage have been confirmed with in vivo animal experiments; hearing recovery in patients with sudden sensorineural hearing loss refractory to systemic glucocorticoid treatment has also been shown to occur following IGF1 treatment. The mechanisms of IGF1-induced maintenance of hair cell number have been investigated using a cochlear explant culture system, which demonstrated that IGF1 acts on supporting cells, leading to the inhibition of hair cell apoptosis and the proliferation of supporting cells. Netrin1 has furthermore been identified as one of the effectors whose expression is increased by IGF1 treatment.
Department of Otolaryngology, Head and Neck Surgery, Graduate School of Medicine, Kyoto University, 54 Shogoin Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan.
Kohei
K
Yamahara
Department of Otolaryngology, Head and Neck Surgery, Graduate School of Medicine, Kyoto University, 54 Shogoin Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan. Electronic address: yamamoto@ent.kuhp.kyoto-u.ac.jp.
Norio
N
Yamamoto
Department of Otolaryngology, Head and Neck Surgery, Graduate School of Medicine, Kyoto University, 54 Shogoin Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan.
Takayuki
T
Nakagawa
Department of Otolaryngology, Head and Neck Surgery, Graduate School of Medicine, Kyoto University, 54 Shogoin Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan.
Juichi
J
Ito
D000287:Administration, Topical; D000617:Aminoglycosides / Q000008:administration & dosage; D000818:Animals; D017209:Apoptosis; D049109:Cell Proliferation; D002986:Clinical Trials as Topic; D003051:Cochlea / Q000187:drug effects / Q000378:metabolism; D007758:Ear, Inner / Q000503:physiopathology; D005938:Glucocorticoids / Q000378:metabolism; D006198:Hair Cells, Auditory / Q000378:metabolism* / Q000502:physiology*; D006319:Hearing Loss, Sensorineural / Q000628:therapy*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000627:therapeutic use*; D009414:Nerve Growth Factors / Q000378:metabolism; D000075388:Netrin-1; D010641:Phenotype; D016032:Randomized Controlled Trials as Topic; D012038:Regeneration / Q000502:physiology*; D015398:Signal Transduction; D013256:Steroids / Q000008:administration & dosage; D025521:Tumor Suppressor Proteins / Q000378:metabolism; D015854:Up-Regulation
D000617:Aminoglycosides; D005938:Glucocorticoids; C583557:IGF1 protein, human; C000617351:NTN1 protein, human; D009414:Nerve Growth Factors; D013256:Steroids; D025521:Tumor Suppressor Proteins; D000075388:Netrin-1; D007334:Insulin-Like Growth Factor I