Modulation of type VII collagen (anchoring fibril) expression by retinoids in human skin cells

We examined the effects of retinoids on the expression of type VII collagen, a major component of anchoring fibrils, in human keratinocytes and amnion cells (WISH). All-trans retinoic acid (RA) (5 x 10(-6) M) decreased the steady-state levels of type VII collagen mRNA by at least 80% after 18 h. The inhibition was evident within 6 h after the addition of RA, maximal at 18 h, and was dose-dependent, Reduction of type VII mRNA expression also occurred when cell cultures were incubated with retinol, retinal, and 13-cis RA. Retinoid-mediated inhibition of type VII collagen mRNA expression was observed in keratinocytes growing in either serum-free keratinocyte growth medium (KGM) or KGM supplemented with 1.4 mM Ca2+. Cycloheximide blocked RA-mediated inhibition of type VII collagen mRNA, demonstrating the need for de novo protein synthesis. The mRNA levels for fibronectin and glyceraldehyde phosphate dehydrogenase were not affected by the retinoids, suggesting selective inhibition on type VII collagen expression. In addition, the decrease in type VII collagen mRNA was accompanied by a parallel decrease in secretion of the 290 kDa, type VII collagen alpha chains.