Suppression of elastin gene expression in dermal fibroblasts by protein phosphatase inhibitor okadaic acid

Treatment of human skin fibroblasts with okadaic acid, an inhibitor of serine/threonine specific protein phosphatases 1 and 2A, resulted in a marked reduction in elastin mRNA levels, with maximal inhibition of 80%. The inhibitory effect of okadaic acid on elastin mRNA levels was efficiently prevented by retinoic acid and cycloheximide and was further enhanced by phorbol ester treatment. Upregulation of elastin mRNA levels by transforming growth factor-beta 2 was abrogated by simultaneous treatment of cells with okadaic acid. Okadaic acid had no effect on the expression of human elastin promoter/CAT chimeric gene in fibroblasts cultured from skin of transgenic mice. These results provide evidence that protein phosphatases 1 and 2A play an important role as positive regulators of elastin gene expression in dermal fibroblasts.