Aging depicts one of the major challenges in pharmacology owing to its complexity and heterogeneity. Thereby, advanced glycated end-products modify extracellular matrix proteins, but the consequences on the skin barrier function remain heavily understudied. Herein, we utilized transmission electron microscopy for the ultrastructural analysis of ribose-induced glycated reconstructed human skin (RHS). Molecular and functional insights substantiated the ultrastructural characterization and proved the relevance of glycated RHS beyond skin aging. In particular, electron microscopy mapped the accumulation and altered spatial orientation of fibrils and filaments in the dermal compartment of glycated RHS. Moreover, the epidermal basement membrane appeared thicker in glycated than in non-glycated RHS, but electron microscopy identified longitudinal clusters of the finest collagen fibrils instead of real thickening. The stratum granulosum contained more cell layers, the morphology of keratohyalin granules decidedly differed, and the stratum corneum lipid order increased in ribose-induced glycated RHS, while the skin barrier function was almost not affected. In conclusion, dermal advanced glycated end-products markedly changed the epidermal morphology, underlining the importance of matrix⁻cell interactions. The phenotype of ribose-induced glycated RHS emulated aged skin in the dermis, while the two to three times increased thickness of the stratum granulosum resembled poorer cornification.

Collegium Medicum Berlin Luisenstr 54 10117 Berlin Germany

Faculty of Pharmacy Charles University Akademika Heyrovského 1203 50005 Hradec Králové Czech Republic

Germany

Institute of Chemistry and Biochemistry Freie Universität Berlin Takustr 3 14195 Berlin Germany

Institute of Pharmacy Freie Universität Berlin Königin Luise Str 2 4 14195 Berlin Germany

Institute of Veterinary Anatomy Department of Veterinary Medicine Freie Universität Berlin Koserstr 20 14195 Berlin Germany

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$a Balansin Rigon, Roberta $u Institute of Pharmacy (Pharmacology & Toxicology), Freie Universität Berlin, Königin-Luise-Str. 2+4, 14195 Berlin, Germany. roberta_rigon@yahoo.com.br.

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$a Ultrastructural and Molecular Analysis of Ribose-Induced Glycated Reconstructed Human Skin / $c R. Balansin Rigon, S. Kaessmeyer, C. Wolff, C. Hausmann, N. Zhang, M. Sochorová, A. Kováčik, R. Haag, K. Vávrová, M. Ulrich, M. Schäfer-Korting, C. Zoschke,

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$a Aging depicts one of the major challenges in pharmacology owing to its complexity and heterogeneity. Thereby, advanced glycated end-products modify extracellular matrix proteins, but the consequences on the skin barrier function remain heavily understudied. Herein, we utilized transmission electron microscopy for the ultrastructural analysis of ribose-induced glycated reconstructed human skin (RHS). Molecular and functional insights substantiated the ultrastructural characterization and proved the relevance of glycated RHS beyond skin aging. In particular, electron microscopy mapped the accumulation and altered spatial orientation of fibrils and filaments in the dermal compartment of glycated RHS. Moreover, the epidermal basement membrane appeared thicker in glycated than in non-glycated RHS, but electron microscopy identified longitudinal clusters of the finest collagen fibrils instead of real thickening. The stratum granulosum contained more cell layers, the morphology of keratohyalin granules decidedly differed, and the stratum corneum lipid order increased in ribose-induced glycated RHS, while the skin barrier function was almost not affected. In conclusion, dermal advanced glycated end-products markedly changed the epidermal morphology, underlining the importance of matrix⁻cell interactions. The phenotype of ribose-induced glycated RHS emulated aged skin in the dermis, while the two to three times increased thickness of the stratum granulosum resembled poorer cornification.

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$a Kaessmeyer, Sabine $u Institute of Veterinary Anatomy, Department of Veterinary Medicine, Freie Universität Berlin, Koserstr. 20, 14195 Berlin, Germany. sabine.kaessmeyer@fu-berlin.de.

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$a Wolff, Christopher $u Institute of Pharmacy (Pharmacology & Toxicology), Freie Universität Berlin, Königin-Luise-Str. 2+4, 14195 Berlin, Germany. christopher.wolff@fu-berlin.de.

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$a Hausmann, Christian $u Institute of Pharmacy (Pharmacology & Toxicology), Freie Universität Berlin, Königin-Luise-Str. 2+4, 14195 Berlin, Germany. christian.hausmann@fu-berlin.de.

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$a Zhang, Nan $u Institute of Pharmacy (Pharmacology & Toxicology), Freie Universität Berlin, Königin-Luise-Str. 2+4, 14195 Berlin, Germany. nan.zhang@fu-berlin.de.

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$a Sochorová, Michaela $u Faculty of Pharmacy, Charles University, Akademika Heyrovského 1203, 50005 Hradec Králové, Czech Republic. sochormi@faf.cuni.cz.

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$a Kováčik, Andrej $u Faculty of Pharmacy, Charles University, Akademika Heyrovského 1203, 50005 Hradec Králové, Czech Republic. kovacika@faf.cuni.cz.

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$a Haag, Rainer $u Institute of Chemistry and Biochemistry, Freie Universität Berlin, Takustr. 3, 14195 Berlin, Germany; Germany. haag@chemie.fu-berlin.de.

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$a Vávrová, Kateřina $u Faculty of Pharmacy, Charles University, Akademika Heyrovského 1203, 50005 Hradec Králové, Czech Republic. katerina.vavrova@faf.cuni.cz.

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$a Ulrich, Martina $u Collegium Medicum Berlin, Luisenstr. 54, 10117 Berlin, Germany. ulrich@dermatologie-am-regierungsviertel.de.

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$a Schäfer-Korting, Monika $u Institute of Pharmacy (Pharmacology & Toxicology), Freie Universität Berlin, Königin-Luise-Str. 2+4, 14195 Berlin, Germany. Monika.Schaefer-Korting@fu-berlin.de.

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$a Zoschke, Christian $u Institute of Pharmacy (Pharmacology & Toxicology), Freie Universität Berlin, Königin-Luise-Str. 2+4, 14195 Berlin, Germany. christian.zoschke@fu-berlin.de.

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