title: 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 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.
authors: L'Oréal, Research & Innovation , Aulnay-sous-bois, France .
authors: Hervé
authors: H
authors: Pageon
authors: L'Oréal, Research & Innovation , Aulnay-sous-bois, France .
authors: Hélène
authors: H
authors: Zucchi
authors: Department of Pathology, Case Western Reserve University , Cleveland, Ohio.
authors: Zhenyu
authors: Z
authors: Dai
authors: Department of Pathology, Case Western Reserve University , Cleveland, Ohio.
authors: David R
authors: DR
authors: Sell
authors: Department of Pathology, Case Western Reserve University , Cleveland, Ohio.
authors: Christopher M
authors: CM
authors: Strauch
authors: Department of Pathology, Case Western Reserve University , Cleveland, Ohio. ; Department of Biochemistry, Case Western Reserve University , Cleveland, Ohio.
authors: Vincent M
authors: VM
authors: Monnier
authors: L'Oréal, Research & Innovation , Aulnay-sous-bois, France .
authors: Daniel
authors: D
authors: Asselineau
keywords: aging; extracellular matrix; glucose; glycation; methylglyoxal; oxoaldehydes