Effect of 1–2 mmol/1 calcium, triamcinolone acetonide, and retinoids on low-calcium regulated keratinocyte differentiation

Abstract

Neonatal mouse keratinocytes cultured in low calcium (001 mmol/1) show rapid growth and little stratification when compared with cells grown in normal 1·2 mmol/1 calcium. The effect of low calcium on the amount and synthesis of specific differentiation proteins was studied; additionally, the effect of 10 -8 mol/1 triamcinolone acetonide, and 6 /Μg/ml of retinoic acid and of etretinate (Ro 10–9359) on low-calcium regulated keratinocyte hyperproliferation and differentiation was determined. Low-calcium regulated keratinocytes contained less non-covalently cross-linked and disulphide cross-linked keratins, less cell envelopes, much greater amounts of SDS-soluble viable cell proteins, and slightly more keratohyaline granule-related proteins than normal-calcium regulated keratinocytes. A 24 h switching time to 1·2 mmol/1 calcium medium did not affect the amounts or synthesis of these proteins. Both retinoids and triamcinolone acetonide inhibited by approximately 50% the proliferation of the low-calcium regulated keratinocytes. Growth of low-calcium cells in these drugs for 9 days increased the amounts of both keratins and cell envelope proteins in the cultures. We concluded that calcium-dependent processes can regulate epidermal keratinocyte proliferation and differentiation. Our studies suggest that these calcium-regulated events may occur via changes in calcium-dependent proteins.