p27Kip1 Knockdown Induces Proliferation in the Organ of Corti in Culture after Efficient shRNA Lentiviral TransductionReportar como inadecuado

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The cells in the organ of Corti do not exhibitspontaneous cell regeneration; hair cells that die afterdamage are not replaced. Supporting cells can beinduced to transdifferentiate into hair cells, but thatwould deplete their numbers, therefore impairingepithelium physiology. The loss of p27Kip1 functioninduces proliferation in the organ of Corti, which raisesthe possibility to integrate it to the strategies to achieveregeneration. Nevertheless, it is not known if the extentof this proliferative potential, as well as its maintenancein postnatal stages, is compatible with providing a basisfor eventual therapeutic manipulation. This is due inpart to the limited success of approaches to deliver toolsto modify gene expression in the auditory epithelium.We tested the hypothesis that the organ of Corti canundergo significant proliferation when efficient manipulationof the expression of regulators of the cell cycle isachieved. Lentiviral vectors were used to transduce allcochlear cell types, with efficiencies around 4%for haircells, 43%in the overall supporting cell population, and74 % within lesser epithelial ridge LER cells.Expression of short hairpin RNA targeting p27Kip1encoded by the lentiviral vectors led to measurableproliferation in the organ of Corti and increase in LERcells number but not hair cell regeneration. Our resultsrevalidate the use of lentiviral vectors in the study and inthe potential therapeutic approaches for inner eardiseases, as well as demonstrate that efficient manipulationof p27Kip1 is sufficient to induce significantproliferation in the postnatal cochlea.Nota general

Artículo de publicación ISI

Autor: Maass Oñate, Juan; - Berndt, F. Andrés; - Cánovas, José; - Kukuljan Padilla, Manuel; -

Fuente: http://repositorio.uchile.cl/


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