title: Insulin-like growth factor 1 induces the transcription of Gap43 and Ntn1 during hair cell protection in the neonatal murine cochlea.
abstract: We previously reported that insulin-like growth factor 1 (IGF-1) protects cochlear hair cells against aminoglycosides through activation of the PI3K/Akt and MEK/ERK pathways in supporting cells. In this study, we found that IGF-1 up-regulated the expression levels of Gap43 and Ntn1 as measured using cDNA microarray analysis and qRT-PCR. Using inhibitors of the PI3K/Akt and MEK/ERK pathways, we reveal that both pathways are involved in the up-regulation of Gap43 and Ntn1 expression. Moreover the time window of Gap43 and Ntn1 transcription was limited to within 12h after IGF-1 treatment, indicating that downstream gene expression was tightly controlled by IGF-1.
authors: 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: y_hayashi@ent.kuhp.kyoto-u.ac.jp.
authors: Yushi
authors: Y
authors: Hayashi
authors: 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.
authors: Norio
authors: N
authors: Yamamoto
authors: 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: tnakagawa@ent.kuhp.kyoto-u.ac.jp.
authors: Takayuki
authors: T
authors: Nakagawa
authors: 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: ito@ent.kuhp.kyoto-u.ac.jp.
authors: Juichi
authors: J
authors: Ito
mesh_terms: D000617:Aminoglycosides / Q000633:toxicity*; D000818:Animals; D000831:Animals, Newborn; D019922:GAP-43 Protein / Q000235:genetics / Q000378:metabolism*; D006198:Hair Cells, Auditory / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism* / Q000494:pharmacology; D008813:Mice, Inbred ICR; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009355:Neomycin / Q000633:toxicity; D009414:Nerve Growth Factors / Q000235:genetics / Q000378:metabolism*; D000075388:Netrin-1; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D015398:Signal Transduction; D014158:Transcription, Genetic; D059467:Transcriptome; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D000617:Aminoglycosides; D019922:GAP-43 Protein; C000617351:NTN1 protein, human; D009414:Nerve Growth Factors; C000617353:Ntn1 protein, mouse; D012333:RNA, Messenger; D011994:Recombinant Proteins; D025521:Tumor Suppressor Proteins; D000075388:Netrin-1; D007334:Insulin-Like Growth Factor I; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D020928:Mitogen-Activated Protein Kinases; D009355:Neomycin
keywords: Adcy7; Cochlea; ERK; Gap43; Growth associated protein 43 (Gap43); IGF-1; Ier5; Insulin-like growth factor 1 (IGF-1); Kitl; MAPK/ERK kinase; MEK; Microarray; Netrin 1 (Ntn1); Ntn1; PI3K; adenylate cyclase 7; extracellular signal-regulated kinase; growth associated protein 43; immediate early response 5; insulin-like growth factor 1; kit ligand; netrin 1; phosphatidylinositol 3-kinase; qRT-PCR; quantitative reverse transcriptase polymerase chain reaction