title: pRb phosphorylation regulates the proliferation of supporting cells in gentamicin-damaged neonatal avian utricle.
abstract: The ability of nonmammalian vertebrates to regenerate hair cells (HCs) after damage-induced HC loss has stimulated and inspired research in the field of HC regeneration. The protein pRb encoded by retinoblastoma gene Rb1 forces sensory progenitor cells to exit cell cycle and maintain differentiated HCs and supporting cells (SCs) in a quiescent state. pRb function is regulated by phosphorylation through the MEK/ERK or the pRb/Raf-1 signaling pathway. In our previous study, we have shown that pRb phosphorylation is crucial for progenitor cell proliferation and survival during the early embryonic stage of avian otocyst sensory epithelium development. However, in damaged avian utricle, the role of pRb in regulating the cell cycling of SCs or HCs regeneration still remains unclear. To further elucidate the function of pRb phosphorylation on SCs re-entering the cell cycle triggered by gentamycin-induced HCs damage, we isolated neonatal chicken utricles and treated them with the MEK inhibitor U0126 or the pRb/Raf-1 inhibitor RRD-251, respectively in vitro. We found that after gentamycin-induced HCs damage, pRb phosphorylation is important for the quiescent SCs re-entering the cell cycle in the neonatal chicken utricle. In addition, the proliferation of SCs decreased in a dose-dependent manner in response to both U0126 and RRD-251, which indicates that both the MEK/ERK and the pRb/Raf-1 signaling pathway play important roles in pRb phosphorylation in damaged neonatal chicken utricle. Together, these findings on the function of pRb in damaged neonatal chicken utricle improve our understanding of the regulation of the cell cycle of SCs after HCs loss and may shed light on the mammalian HC regeneration from SCs in damaged organs.
authors.affiliation: aDepartment of Otorhinolaryngology bResearch Center, Affiliated Eye and ENT Hospital of Fudan University cInstitute of Stem Cell and Regeneration Medicine, Institutions of Biomedical Science dState Key Laboratory of Medical Neurobiology, Fudan University, Shanghai, China.
authors.forename: Jingfang
authors.initials: J
authors.lastname: Wu
authors.forename: Shan
authors.initials: S
authors.lastname: Sun
authors.forename: Wenyan
authors.initials: W
authors.lastname: Li
authors.forename: Yan
authors.initials: Y
authors.lastname: Chen
authors.forename: Huawei
authors.initials: H
authors.lastname: Li
mesh_terms: D000818:Animals; D030161:Avian Proteins / Q000378:metabolism*; D002070:Butadienes / Q000494:pharmacology; D002453:Cell Cycle / Q000187:drug effects / Q000502:physiology*; D049109:Cell Proliferation / Q000187:drug effects / Q000502:physiology*; D002645:Chickens; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005839:Gentamicins / Q000633:toxicity; D006198:Hair Cells, Auditory / Q000187:drug effects / Q000502:physiology; D020930:MAP Kinase Kinase Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D009570:Nitriles / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D019908:Proto-Oncogene Proteins c-raf / Q000037:antagonists & inhibitors / Q000378:metabolism; D016160:Retinoblastoma Protein / Q000378:metabolism*; D012444:Saccule and Utricle / Q000187:drug effects / Q000503:physiopathology*; D013890:Thiourea / Q000031:analogs & derivatives / Q000494:pharmacology; D046509:Tissue Culture Techniques
chemical_list: D030161:Avian Proteins; D002070:Butadienes; D004791:Enzyme Inhibitors; D005839:Gentamicins; D009570:Nitriles; C556907:RRD 251; D016160:Retinoblastoma Protein; C113580:U 0126; D019908:Proto-Oncogene Proteins c-raf; D020930:MAP Kinase Kinase Kinases; D013890:Thiourea