Retinoid reversal of squamous metaplasia in organ cultures of tracheas derived from hamsters fed on vitamin A-deficient diet

Abstract

Cytokinetic and ultrastructural studies were carried out to elucidate mechanisms involved in the reversal of squamous metaplasia (SM) by β-retinoic acid in organ cultures of tracheas derived from vitamin A-deficient hamsters. Tracheal cultures exhibiting focal areas of SM were treated with the retinoid for up to 7 days. The retinoid significantly inhibited [ 3 H]-thymidine labeling indices in the basal cells and stimulated the labeling indices in mucous cells. At the ultrastructural level the retinoid induced marked remodeling alterations in the metaplastic epithelium that included: (a) disruption of desmosomes and widening of intercellular spaces; (b) extensive vacuolation and degeneration of the metaplastic cells; (c) extrusion of the degenerated cells; (d) aggregation of keratin filaments; and (e) differentiation of certain basal cells into secretory cells. Consequently most degenerated metaplastic cells were extruded and the epithelium repopulated as a result of differentiation of basal cells into mucous cells and hyperplasia of the pre-existing mucous cells. The degenerative effects of the retinoid were limited to the metaplastic foci since the uninvolved epithelium adjoining metaplastic foci were not significantly altered. The results suggest that the restoration of normal tracheal epithelium following the retinoid treatment of explants exhibiting focal areas of squamous metaplasia is associated with the enhanced proliferation of the mucous cells. The inhibition of proliferation of basal cells further prevented hyperplasia and restored cell replication within the normal range.