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

• Published in: Clinica chimica acta Vol. 362; no. 1; pp. 161 - 169
• Main Authors: Kim, Mi-Sun, Lee, SeRah, Rho, Ho Sik, Kim, Duck Hee, Chang, Ih Seop, Chung, Jin Ho
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.12.2005
• Subjects: Adult; Aged; Aging; Dioxolanes - chemical synthesis; Dioxolanes - chemistry; Dioxolanes - pharmacology; Extracellular matrix; Extracellular Matrix Proteins - metabolism; Female; Gene Expression Regulation - drug effects; Humans; Male; Matrix metalloproteinase; Matrix Metalloproteinase 1 - metabolism; Molecular Structure; Proto-Oncogene Proteins c-jun - metabolism; Pyrans - chemical synthesis; Pyrans - chemistry; Pyrans - pharmacology; Retinoid; Retinoids - chemical synthesis; Retinoids - chemistry; Retinoids - pharmacology; Skin Aging - drug effects; Skin Aging - radiation effects; Skin irritation; Tretinoin - pharmacology; UV; tRA; RAR; EI; Retinoid; Skin irritation; Matrix metalloproteinase; AP-1; MED; ECM; LDF; MMP-1; Aging; Extracellular matrix
• ISSN: 0009-8981; 1873-3492
• DOI: 10.1016/j.cccn.2005.06.016

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. 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. 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. 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.