Biological Effects Induced by Specific Advanced Glycation End Products in the Reconstructed Skin Model of Aging
Abstract Advanced glycation end products (AGEs) accumulate in the aging skin. To understand the biological effects of individual AGEs, skin reconstructed with collagen selectively enriched with Ne (carboxymethyl) lysine (CML) Ne (carboxyethyl) lysine (CEL) methylglyoxal hydroimidazolone (MG H1) or pentosidine was studied. Immunohistochemistry revealed increased expression of a6 integrin at the dermal epidermal junction by CEL and CML (p<0.01) Laminin 5 was diminished by CEL and MG H1 (p<0.05) Both CML and CEL induced a robust increase (p<0.01) in procollagen I. In the culture medium, IL 6, VEGF, and MMP1 secretion were significantly decreased (p<0.05) by MG H1. While both CEL and CML decreased MMP3, only CEL decreased IL 6 and TIMP1, while CML stimulated TIMP1 synthesis significantly (p<0.05) mRNA expression studies using qPCR in the epidermis layer showed that CEL increased type 7 collagen (COL7A1) b1, and a6 integrin, while CML increased only COL7A1 (p<0.05) MG H1 modified collagen had no effect. Importantly, in the dermis layer, MMP3 mRNA expression was increased by both CML and MG H1. CML also significantly increased the mRNAs of MMP1, TIMP1, keratinocyte growth factor (KGF) IL 6, and monocyte chemoattractant protein 1 (MCP1) (p<0.05) Mixed effects were present in CEL rich matrix. Minimally glycoxidized pentosidine rich collagen suppressed most mRNAs of the genes studied (p<0.05) and decreased VEGF and increased MCP1 protein expression. Taken together, this model of the aging skin suggests that a combination of AGEs tends to counterbalance and thus minimizes the detrimental biological effects of individual AGEs.
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