All-trans-retinoic acid enhances collagen gene expression in irradiated and non-irradiated hairless mouse skin.

ABSTRACT

All-trans-retinoic acid (t-RA) can repair some of the tissue damage caused by chronic exposure of skin to UV radiation. In the present study, we have investigated its effect on collagen and collagenase gene expression in hairless mouse skin. Hairless mice (SKH-hr 1) were irradiated 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 treatment. In our experimental conditions, UVB irradiation alone induced no changes in type I, III and VI collagen mRNA levels in dorsal and ventral skin. The mRNA level of collagenase I was also unchanged. Topically applied t-RA increased the steady state levels of type I and III collagen mRNA in irradiated and non-irradiated dorsal skin. The mean increase 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 alpha 1(I) and alpha 1(III) mRNA. The mRNA level of type VI collagen was also significantly increased by t-RA, but only in irradiated skin. The mRNA level of collagenase was significantly decreased only in irradiated t-RA-treated skin. In addition, t-RA exerted a systemic effect because 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 leads to the conclusion that topical t-RA exerts directly and/or indirect effects on the expression of collagen genes in irradiated and non-irradiated hairless mouse skin.