ALL-TRANS-RETINOIC ACID ENHANCES COLLAGEN GENE-EXPRESSION IN IRRADIATED AND NONIRRADIATED HAIRLESS MOUSE SKIN

All-trans-retinoic acid (t-RA) can repair some of the tissue damage ca used by chronic exposure of skin to UV radiation. In the present study , we have investigated its effect on collagen and collagenase gene exp ression in hairless mouse skin. Hairless mice (SKH-hr 1) were irradiat ed dorsally with increasing doses of UVB radiation (total, 4.8 J cm(-2 )) for 10 weeks. The animals were then topically treated with 0.05% t- RA dissolved in a vehicle or with the vehicle alone three times a week for up to 10 weeks. Non-irradiated animals underwent the same treatme nt. In our experimental conditions, UVB irradiation alone induced no c hanges in type I, III and VI collagen mRNA levers in dorsal and ventra l skin. The mRNA level of collagenase I was also unchanged. Topically applied t-RA increased the steady state levels of type I and III colla gen mRNA in irradiated and non-irradiated dorsal skin. The mean increa se was about 2.2- and 2.7-fold in non-irradiated skin and 2.4- and 2.5 -fold in irradiated skin for type I and III collagen mRNA respectively . The increase in irradiated skin was partly due to the vehicle alone, which exerted a stimulating effect on the steady state levels of alph a 1(I) and alpha 1(III) mRNA. The mRNA level of type VI collagen was a lso significantly increased by t-RA, but only in irradiated skin. The mRNA level of collagenase was significantly decreased only in irradiat ed t-RA-treated skin. In addition, t-RA exerted a systemic effect beca use the mRNA levels of collagen were enhanced by factors of 1.9 and 2. 5 for alpha 1(I) and 2.0 and 2.0 for alpha 1(III) in the ventral skin of irradiated and non-irradiated animals respectively. This study lead s to the conclusion that topical t-RA exerts direct and/or indirect ef fects on the expression of collagen genes in irradiated and non-irradi ated hairless mouse skin.