Inhibition of tropoelastin expression by 1, 25-dihydroxyvitamin d₃

Elastin production is modulated by steroid hormones and is dependent on calcium. Because vitamin D₃ is involved in the regulation of calcium metabolism and influences the expression of various extracellular matrix proteins, we investigated whether vitamin D₃ influences tropoelastin expression. Three elastin-producing, bovine cell types, auricular chondroblasts, nuchal ligament fibroblasts and arterial smooth muscle cells, were treated with the principal active metabolite of vitamin D₃, 1, 25-dihydroxyvitamin D₃ (l, 25[OH]₂ D₃), and with 24, 25 dihydroxy-vitamin D₃ (24, 25[OH]₂ D₃). Tropoelastin levels in culture media and cell layers, as measured by an enzyme-linked immunoassay, decreased in a dose and exposure dependent manner after treatment with 1, 25(OH)₂ D₃; 24, 25(OH)₂ D₃ had no effect on tropoelastin production relative to solvent-treated controls. The maximal effective dose of l, 25(OH)₂ D₃ was 10^-7 M for 48 hr, which resulted in a severalfold reduction of tropoelastin production, and decreased tropoelastin levels were detected at 8 hr after treatment. Reduction of tropoelastin protein production was paralleled by a decrease of equal magnitude in the steady-state levels of tropoelastin mRNA. Vitamin D₃metabolites had no effect on DNA or total protein synthesis. These results suggest that vitamin D₃ may be an important modulator of elastin expression.