Regulation of Differentiation of Tracheal Epithelial Cells by Retinoids

Epithelial cells of the airways can, under pathological conditions, undergo squamous metaplasia. The accumulation of cholesterol sulfate has recently been described as a new marker for squamous cell differentiation in rabbit tracheal epithelial cells. We now report that normal human bronchial epithelial cells in culture metabolically incorporated [35S]-sulfate and [3H]-mevalonate into material indistinguishable from cholesterol sulfate by the criteria of solubility in organic solvents, behavior on ion-exchange chromatography, susceptibility to solvolysis, and behavior on thin-layer chromatography before and after solvolysis. The accumulation of cholesterol [35S]-sulfate correlated well with squamous cell differentiation (as measured by cross-linked envelope formation), which occurred when the cells reached confluency. The increase in the level of cholesterol sulfate could be inhibited by the inclusion of retinoic acid in the cell-culture medium. The addition of phorbol-12-myristate-13-acetate or the presence of high Ca2+ concentration in the medium stimulated the accumulation of cholesterol sulfate. An increased activity of cholesterol sulfotransferase seems to account for the cholesterol sulfate accumulation. The original observation of cholesterol sulfate accumulation during squamous differentiation thus extends across species lines and strengthens the suggestion that the cholesterol sulfate may play an important role in this type of differentiation. Moreover, cholesterol sulfate provides a sensitive biochemical marker to study this pathway of differentiation of human bronchial epithelial cells.

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Effects of vitamin A on proliferation of human distal airway epithelial cells in culture

Shibagaki

Kitamura

Inayama

et al. 1994

Vichows Archiv A Pathol Anat

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Using a serum-free culture method, we investigated the effects of vitamin A on the proliferation of human distal airway epithelial cells. Outgrowth of epithelial cells from lung tissue explants was enhanced by treatment with all-trans retinol at concentrations of 10(-8) to 10(-7) M. The colony-forming activity of cells harvested from the primary culture and replated onto Swiss 3T3 fibroblastic feeders was, in contrast, significantly reduced by 10(-7) M to 10(-5) M retinol. When the primary cells were harvested and subcultured on Primaria plates, population expansion was also inhibited by retinol at 10(-10) to 10(-6) M. We further investigated the cells to determine whether there was any difference in sensitivity to the growth-inhibitory effects of vitamin A between cells from the primary culture incubated with and without retinol. The population increase in cells harvested from the primary culture was inhibited equally in retinol-treated and non-treated cells by subsequent treatment with retinol or retinoic acid, this inhibition being dose-dependent. DNA synthetic activity was also inhibited. Interestingly, both the growth rate and the colony-forming efficiency on feeders were greater in the subculture of cells from the retinol-treated primary culture than in those non-treated. When the cells in the secondary subculture were treated with retinoic acid and replated again, they showed a greater population increase rate than those non-treated. Our results showed that human distal airway epithelial cells isolated from lung tissue were sensitive to the growth-inhibitory effect of vitamin A, but the proliferative potential in some fraction of the epithelial cell population was possibly enhanced by vitamin A treatment.

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Regulation of Differentiation of Tracheal Epithelial Cells by Retinoids

Cited by 14 publications

References 22 publications

Inhibition of Epidermal Terminal Differentiation and Tumour Promotion by Retinoids

Inhibition of Epidermal Terminal Differentiation and Tumour Promotion by Retinoids

Human bronchial epithelial cells synthesize cholesterol sulfate during squamous differentiation in vitro

Effects of vitamin A on proliferation of human distal airway epithelial cells in culture

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