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 col lagen, a major component of anchoring fibrils, in human keratinocytes and amnion cells (WISH). All-trans retinoic acid (RA) (5 x 10(-6) M) d ecreased 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 addit ion of RA, maximal at 18 h, and was dose-dependent, Reduction of type VII mRNA expression also occurred when cell cultures were incubated wi th retinol, retinal, and 13-cis RA. Retinoid-mediated inhibition of ty pe VII collagen mRNA expression was observed in keratinocytes growing in either serum-free keratinocyte growth medium (KGM) or KGM supplemen ted with 1.4 mM Ca2+. Cycloheximide blocked RA-mediated inhibition of type VII collagen mRNA, demonstrating the need for de novo protein syn thesis. The mRNA levels for fibronectin and glyceraldehyde phosphate d ehydrogenase 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 se cretion of the 290 kDa, type VII collagen alpha chains.