Background Although retinoids have potential efficacy in aged skin, their side effect (skin irritation) remains a clinical problem. We designed a novel synthetic retinoid, seletinoid G, by using computer-aided molecular modeling, and investigated its effects on the expression of extracellular matrix proteins in human skin in vivo. Methods Twenty-three subjects were tested on the buttocks using 4-day occlusive application of seletinoid G and all- trans retinoic acid ( t RA). Skin irritation after topical application was quantified by the degree of erythema and cutaneous blood flow. The expression of extracellular matrix proteins and interstitial collagenase (MMP-1) in skin biopsies was investigated by immunohistochemical staining and Western blotting. Results The topical application of seletinoid G under occlusion induced no skin irritation in contrast to t RA, which caused severe erythema. The topical treatment with seletinoid G increased the expressions of type I procollagen, tropoelastin, and fibrillin-1, and reduced MMP-1 in old skin in vivo. Seletinoid G was found to inhibit not only the UV-induced decrease of type I procollagen but the UV-induced increase of MMP-1 and c-Jun protein in young skin in vivo. Conclusions Seletinoid G is a novel synthetic retinoid, which has little the side effect of skin irritation after topical application. Seletinoid G can repair altered connective tissue in old skin and inhibit UV-induced collagen deficiency in young skin.
