title: Transdifferentiation of vocal-fold stellate cells and all-trans retinol-induced deactivation.
abstract: The maculae flavae of the human vocal folds include dense extracellular matrices and compacted cells with a stellate morphology. These vocal-fold stellate cells are thought to participate in the metabolism of extracellular matrices essential in maintaining vocal-fold viscoelasticity required for phonation. We have isolated and cultured these new cells and have tested the hypothesis that they maintain a distinct cellular and biochemical phenotype. We have compared proliferation rates, changes on immunophenotype, and intracellular lipid and vitamin A storage. Vocal-fold stellate cells undergo culture-induced transdifferentiation to a myofibroblast-like phenotype with an altered phenotype resembling, but not identical to, activated hepatic and pancreatic stellate cells. Our results reveal that these cells are capable of responding to exogenous all-trans retinol in culture. Exposure to this synthetic co-factor causes deactivation characterized by decreased proliferation, loss of the activated stellate cell marker, alpha-smooth muscle actin, and restoration of intracellular lipid and vitamin A metabolite storage. These data establish a new and distinct cellular target for future investigations of the viscoelastic properties of the vocal-fold mucosa during normal phonation, aging, vocal-fold scarring, laryngeal fibrosis, and myofibroblastoma.
authors.affiliation: National Center for Voice and Speech, Department of Speech Pathology and Audiology, University of Iowa, 330 Wendell Johnson Speech and Hearing Center, IA 52242, Iowa City, USA. tannin-fuja@uiowa.edu
authors.forename: Tannin J
authors.initials: TJ
authors.lastname: Fuja
authors.forename: Megan N
authors.initials: MN
authors.lastname: Probst-Fuja
authors.forename: Ingo R
authors.initials: IR
authors.lastname: Titze
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D007820:Laryngeal Mucosa / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D013552:Swine; D014801:Vitamin A / Q000494:pharmacology*; D014827:Vocal Cords / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism
chemical_list: D014801:Vitamin A