Open AccessBiological Effects Induced by Specific Advanced Glycation End Products in the Reconstructed Skin Model of Aging
Author(s) -
Hervé Piégay,
Hélène Zucchi,
Zhen Dai,
David R. Sell,
Christopher Strauch,
Vincent M. Monnier,
Daniel Asselineau
Publication year - 2015
Publication title -
bioresearch open access
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.457
H-Index - 26
eISSN - 2164-7860
pISSN - 2164-7844
DOI - 10.1089/biores.2014.0053
Subject(s) - pentosidine , chemistry , mmp3 , mmp1 , timp1 , glycation , fibronectin , dermis , decorin , integrin , endocrinology , medicine , microbiology and biotechnology , extracellular matrix , gene expression , biochemistry , biology , receptor , anatomy , proteoglycan , gene
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 N(ɛ)-(carboxymethyl)-lysine (CML), N(ɛ)-(carboxyethyl)-lysine (CEL), methylglyoxal hydroimidazolone (MG-H1), or pentosidine was studied. Immunohistochemistry revealed increased expression of α6 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), β1, and α6 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.