title: Cotransfection of Pax2 and Math1 promote in situ cochlear hair cell regeneration after neomycin insult.
abstract: The ideal strategy for hair cell regeneration is promoting residual supporting cell proliferation followed by induction of hair cell differentiation. In this study, cultured neonatal mouse organs of Corti were treated with neomycin to eliminate hair cells followed by incubation with recombined adenovirus expressing Pax2 and/or Math1. Results showed that overexpression of Pax2 significantly promoted proliferation of supporting cells. The number of BrdU⁺/myosin VIIA⁺ cells increased significantly in hair cell pre-existing region two weeks after adenovirus infection in Ad-Pax2-IRES-Math1 group compared to Ad-Pax2 and Ad-Math1 groups. This indicated that cotransfection of Pax2 and Math1 induced supporting cells to proliferate and differentiate into hair cells in situ. Most new hair cells were labeled by FM1-43 suggesting they acquired certain function. The results also suggest that inducing proliferating cells rather than quiescent cells to differentiate into hair cells by forced expression of Math1 is feasible for mammalian hair cell regeneration.
authors.affiliation: 1] Otology Skull base Surgery Department, Hearing Research Institute, Eye and ENT Hospital of Shanghai Medical School, Fudan University. Shanghai, 200031, P.R.China [2] Central laboratory, Eye and ENT Hospital of Shanghai Medical School, Fudan University. Shanghai, 200031, P.R.China [3].
authors.forename: Yan
authors.initials: Y
authors.lastname: Chen
authors.forename: Huiqian
authors.initials: H
authors.lastname: Yu
authors.forename: Yanping
authors.initials: Y
authors.lastname: Zhang
authors.forename: Wen
authors.initials: W
authors.lastname: Li
authors.forename: Na
authors.initials: N
authors.lastname: Lu
authors.forename: Wenli
authors.initials: W
authors.lastname: Ni
authors.forename: Yingzi
authors.initials: Y
authors.lastname: He
authors.forename: Jin
authors.initials: J
authors.lastname: Li
authors.forename: Shan
authors.initials: S
authors.lastname: Sun
authors.forename: Zhengmin
authors.initials: Z
authors.lastname: Wang
authors.forename: Huawei
authors.initials: H
authors.lastname: Li
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D000900:Anti-Bacterial Agents / Q000633:toxicity*; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics*; D049109:Cell Proliferation; D004848:Epithelium / Q000378:metabolism; D015870:Gene Expression; D018014:Gene Transfer Techniques; D005822:Genetic Vectors / Q000235:genetics; D006198:Hair Cells, Auditory / Q000187:drug effects* / Q000502:physiology*; D006801:Humans; D007231:Infant, Newborn; D051379:Mice; D009355:Neomycin / Q000633:toxicity*; D009925:Organ of Corti / Q000187:drug effects / Q000378:metabolism; D051762:PAX2 Transcription Factor / Q000235:genetics*; D012038:Regeneration; D014162:Transfection
chemical_list: D000900:Anti-Bacterial Agents; D051792:Basic Helix-Loop-Helix Proteins; D009355:Neomycin; D051762:PAX2 Transcription Factor; C500943:Atoh1 protein, mouse