Transforming growth factor-alpha-induced cellular changes in organotypic cultures of juvenile, amikacin-treated rat organ of corti.
Hair cell losses in the mammalian cochlea following an ototoxic insult are irreversible. However, past studies have shown that amikacin treatment in rat cochleae resulted in the transient presence of atypical Deiters' cells (ACs) in the damaged organ of Corti. These ACs arise through a transformation of Deiters' cells, which produce, at their apical pole, densely packed microvilli reminiscent of early-differentiating stereociliary bundles. The ACs do not, however, express typical hair cell markers such as parvalbumin or calbindin. The present study was designed to determine whether specific growth factors could influence the survival and differentiation of these ACs and stimulate hair cell regeneration processes in vitro. Apical-medial segments of organ of Corti of juvenile amikacin-treated rats were established as organotypic cultures, and the effects of epidermal growth factor (EGF), insulin-like growth factor 1 (IGF-1), transforming growth factor-alpha (TGFalpha), and retinoic acid were studied using morphological and molecular approaches. Our results indicate that TGFalpha supports the survival of the damaged organ of Corti and influences ACs differentiation in vitro, possibly acting through reorganization of the actin cytoskeleton. These effects could be directly mediated through activation of the EGF receptor, which is expressed by supporting cells in the mature organ of Corti. TGFalpha does not, however, allow the ACs to progress towards a hair cell phenotype.
Daudet
Nicolas
N
INSERM UR 254, Université Montpellier I, 71 rue de Navacelles, 34090 Montpellier, France. daudet@montp.inserm.fr
Ripoll
Chantal
C
Lenoir
Marc
M
D000199:Actins / Q000187:drug effects / Q000378:metabolism; D000583:Amikacin / Q000633:toxicity; D000818:Animals; D000900:Anti-Bacterial Agents / Q000633:toxicity; D001973:Bromodeoxyuridine; D002454:Cell Differentiation / Q000187:drug effects* / Q000502:physiology; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects* / Q000502:physiology; D004815:Epidermal Growth Factor / Q000378:metabolism / Q000494:pharmacology; D006198:Hair Cells, Auditory / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D007150:Immunohistochemistry; D007334:Insulin-Like Growth Factor I / Q000378:metabolism / Q000494:pharmacology; D008854:Microscopy, Electron; D008855:Microscopy, Electron, Scanning; D009410:Nerve Degeneration / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D009416:Nerve Regeneration / Q000187:drug effects* / Q000502:physiology; D009457:Neuroglia / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D009498:Neurotoxins / Q000633:toxicity*; D009924:Organ Culture Techniques; D051381:Rats; D017208:Rats, Wistar; D016211:Transforming Growth Factor alpha / Q000378:metabolism / Q000494:pharmacology*; D014212:Tretinoin / Q000378:metabolism / Q000494:pharmacology
D000199:Actins; D000900:Anti-Bacterial Agents; D009498:Neurotoxins; D016211:Transforming Growth Factor alpha; D014212:Tretinoin; D004815:Epidermal Growth Factor; D007334:Insulin-Like Growth Factor I; D000583:Amikacin; D001973:Bromodeoxyuridine