title: LOXL as a target to increase the elastin content in adult skin: a dill extract induces the LOXL gene expression.
abstract: The lysyl oxidases lysyl oxidase (LOX) and lysyl oxidase-like (LOXL) are responsible for elastin cross-linking. It was shown recently that LOXL is essential for the elastic fibres homeostasis and for their maintenance at adult age. We first determined whether or not elastin, LOX and LOXL are less expressed during adulthood. The LOX and LOXL mRNA level, quantified by real-time reverse transcriptase-polymerase chain reaction decreased in adult skin fibroblasts compared with fibroblasts from children. In contrast, the elastin mRNA level remains stable at all ages. The goal of this study was to induce elastogenesis at the adult age. Therefore, both enzymes, and in particular LOXL, of which expression is the most affected by age, could be targeted to induce elastogenesis in adult skin. We screened a library of about 1000 active ingredients to find activators capable to stimulate specifically the LOXL gene expression in adult dermal fibroblasts. The positive effect of selected active ingredients was confirmed on fibroblasts grown on monolayers and on dermal and skin equivalent cultures. One extract, obtained from dill (LYS'LASTINE V, Engelhard, Lyon, France), stimulates the LOXL gene expression in dermal equivalents (+64% increase in the LOXL mRNA level when compared with control). At the same time, the elastin detection is increased in dermal equivalents and under the dermal-epidermal junction of skin equivalents, without increase of the elastin mRNA. In conclusion, LOXL can be considered as a new target to reinduce elastogenesis. Its stimulation by a dill extract is correlated with increased elastin detection, suggesting an increase in elastogenesis efficiency.
authors.affiliation: Laboratoire des Substituts Cutanés, Hôpital E. Herriot, Lyon, France.
authors.forename: Valérie
authors.initials: V
authors.lastname: Cenizo
authors.forename: Valérie
authors.initials: V
authors.lastname: André
authors.forename: Corinne
authors.initials: C
authors.lastname: Reymermier
authors.forename: Pascal
authors.initials: P
authors.lastname: Sommer
authors.forename: Odile
authors.initials: O
authors.lastname: Damour
authors.forename: Eric
authors.initials: E
authors.lastname: Perrier
mesh_terms: D000328:Adult; D000368:Aged; D000594:Amino Acid Oxidoreductases / Q000378:metabolism*; D028524:Anethum graveolens / Q000378:metabolism*; D002648:Child; D004549:Elastin / Q000737:chemistry*; D005347:Fibroblasts / Q000201:enzymology; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D008875:Middle Aged; D008954:Models, Biological; D010936:Plant Extracts; D008249:Protein-Lysine 6-Oxidase / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D012867:Skin / Q000201:enzymology*
chemical_list: D010936:Plant Extracts; D012333:RNA, Messenger; D004549:Elastin; D000594:Amino Acid Oxidoreductases; C445313:LOXL1 protein, human; D008249:Protein-Lysine 6-Oxidase