EFFECTS OF ALL-TRANS-RETINOIC ACID ON GLYCOSAMINOGLYCAN SYNTHESIS IN PHOTODAMAGED HAIRLESS MOUSE SKIN

All-trans retinoic acid (tRA) was previously shown to be active in wri nkle reduction in the hairless mouse photoaging model. To address the questions of whether tRA also alters glycosaminoglycan (GAG) synthesis and whether observed wrinkle effacement can be attributed to changes in total GAG production, the effects of tRA on de novo GAG synthesis w ere examined in this model. Sulfated glycosaminoglycans (S-GAG) and th e non-sulfated hyaluronic acid (HA) labeled with [H-3]-glucosamine or [S-35]-sulfate were found to diffuse differentially into the medium du ring the labeling period in the control animals (9% and 35% of total i ncorporated label for HA and S-GAG, respectively). Furthermore, the di ffusion of HA into media was significantly changed after tRA treatment (from 9% to 24%), but no alteration was observed in the diffusion of S-GAG. Separation of epidermis and dermis indicated that the additiona l HA in medium after retinoid treatment primarily originated from the dermis. When incorporated label from the medium and skin fractions was combined, both labeling protocols revealed that 10 weeks of tRA treat ment did not increase the total (medium plus skin) de novo synthesis o f either HA or S-GAG. Wrinkle effacement as induced by retinoids in th e photodamaged mouse skin therefore can not be related to an increased total GAG synthesis.