The effects of a novel synthetic retinoid, seletinoid G, on the expression of extracellular matrix proteins in aged human skin in vivo

Abstract

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 ( tRA). 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 tRA, 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.