title: In vitro glycation of an endothelialized and innervated tissue-engineered skin to screen anti-AGE molecules.
abstract: Glycation is one of the major processes responsible for skin aging through induction of the detrimental formation of advanced glycation end-products (AGEs). We developed an innovative tissue-engineered skin combining both a capillary-like and a nerve networks and designed a protocol to induce continuous AGEs formation by a treatment with glyoxal. We determined the optimal concentration of glyoxal to induce AGEs formation identified by carboxymethyl-lysin expression while keeping their toxic effects low. We showed that our tissue-engineered skin cultured for 44 days and treated with 200 μm glyoxal for 31 days displayed high carboxymethyl-lysine expression, which induced a progressively increased alteration of its capillary and nerve networks between 28 and 44 days. Moreover, it produced an epidermal differentiation defect evidenced by the lack of loricrin and filaggrin expression in the epidermis. These effects were almost completely prevented by addition of aminoguanidine 1.5 mm, an anti-glycation compound, and only slightly decreased by alagebrium 500 μm, an AGE-breaker molecule. This tissue-engineered skin model is the first one to combine a capillary and nerve network and to enable a continuous glycation over a long-term culture period. It is a unique tool to investigate the effects of glycation on skin and to screen new molecules that could prevent AGEs formation.
authors.affiliation: Centre LOEX de l'Université Laval, Centre de recherche du CHU de Québec, 1401, 18e Rue, Québec, QC G1J 1Z4, Canada; Département de Chirurgie, Faculté de Médecine, Université Laval, Québec, QC, Canada.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Cadau
authors.affiliation: BASF Beauty Care Solutions, 32 Rue Saint Jean de Dieu, Lyon 69007, France.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Leoty-Okombi
authors.affiliation: BASF Beauty Care Solutions, 32 Rue Saint Jean de Dieu, Lyon 69007, France.
authors.forename: Sabine
authors.initials: S
authors.lastname: Pain
authors.affiliation: BASF Beauty Care Solutions, 32 Rue Saint Jean de Dieu, Lyon 69007, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Bechetoille
authors.affiliation: BASF Beauty Care Solutions, 32 Rue Saint Jean de Dieu, Lyon 69007, France.
authors.forename: Valérie
authors.initials: V
authors.lastname: André-Frei
authors.affiliation: Centre LOEX de l'Université Laval, Centre de recherche du CHU de Québec, 1401, 18e Rue, Québec, QC G1J 1Z4, Canada; Département de Chirurgie, Faculté de Médecine, Université Laval, Québec, QC, Canada. Electronic address: francois.berthod@fmed.ulaval.ca.
authors.forename: François
authors.initials: F
authors.lastname: Berthod
mesh_terms: D000818:Animals; D002196:Capillaries / Q000187:drug effects; D002417:Cattle; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D003094:Collagen / Q000494:pharmacology; D003599:Cytoskeleton / Q000187:drug effects / Q000378:metabolism; D020405:Dermis / Q000098:blood supply / Q000187:drug effects; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects; D000091344:Filaggrin Proteins; D017127:Glycation End Products, Advanced / Q000037:antagonists & inhibitors*; D006031:Glycosylation / Q000187:drug effects; D006037:Glyoxal / Q000494:pharmacology; D006146:Guanidines / Q000494:pharmacology; D006801:Humans; D015603:Keratinocytes / Q000166:cytology / Q000187:drug effects; D008239:Lysine / Q000031:analogs & derivatives / Q000378:metabolism; D051379:Mice; D009474:Neurons / Q000166:cytology / Q000187:drug effects; D020011:Protective Agents / Q000494:pharmacology; D012867:Skin / Q000187:drug effects / Q000294:innervation*; D013844:Thiazoles / Q000494:pharmacology; D023822:Tissue Engineering / Q000379:methods*
chemical_list: C000717249:FLG protein, human; D000091344:Filaggrin Proteins; D017127:Glycation End Products, Advanced; D006146:Guanidines; D020011:Protective Agents; D013844:Thiazoles; D006037:Glyoxal; C048496:N(6)-carboxymethyllysine; D003094:Collagen; C406794:alagebrium; D008239:Lysine; C004479:pimagedine
keywords: Advanced glycation end products; Angiogenesis; Carboxymethyl lysine; Glyoxal; Skin