title: Effects of non-ablative fractional erbium glass laser treatment on gene regulation in human three-dimensional skin models.
abstract: Clinical experiences with non-ablative fractional erbium glass laser therapy have demonstrated promising results for dermal remodelling and for the indications of striae, surgical scars and acne scars. So far, molecular effects on human skin following treatment with these laser systems have not been elucidated. Our aim was to investigate laser-induced effects on skin morphology and to analyse molecular effects on gene regulation. Therefore, human three-dimensional (3D) organotypic skin models were irradiated with non-ablative fractional erbium glass laser systems enabling qRT-PCR, microarray and histological studies at same and different time points. A decreased mRNA expression of matrix metalloproteinases (MMPs) 3 and 9 was observed 3 days after treatment. MMP3 also remained downregulated on protein level, whereas the expression of other MMPs like MMP9 was recovered or even upregulated 5 days after irradiation. Inflammatory gene regulatory responses measured by the expression of chemokine (C-X-C motif) ligands (CXCL1, 2, 5, 6) and interleukin expression (IL8) were predominantly reduced. Epidermal differentiation markers such as loricrin, filaggrin-1 and filaggrin-2 were upregulated by both tested laser optics, indicating a potential epidermal involvement. These effects were also shown on protein level in the immunofluorescence analysis. This novel standardised laser-treated human 3D skin model proves useful for monitoring time-dependent ex vivo effects of various laser systems on gene expression and human skin morphology. Our study reveals erbium glass laser-induced regulations of MMP and interleukin expression. We speculate that these alterations on gene expression level could play a role for dermal remodelling, anti-inflammatory effects and increased epidermal differentiation. Our finding may have implications for further understanding of the molecular mechanism of erbium glass laser-induced effects on human skin.
authors.affiliation: Department of Dermatology and Allergology, RWTH Aachen University, Pauwelsstrasse 30, 52074, Aachen, Germany. pamann@ukaachen.de.
authors.forename: Philipp M
authors.initials: PM
authors.lastname: Amann
authors.affiliation: Department of Dermatology and Allergology, RWTH Aachen University, Pauwelsstrasse 30, 52074, Aachen, Germany.
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Marquardt
authors.affiliation: Department of Oral and Maxillofacial Surgery, Medical Faculty, RWTH Aachen University, Aachen, Germany.|Interdisciplinary Center for Laser Medicine, RWTH Aachen University, Aachen, Germany.
authors.forename: Timm
authors.initials: T
authors.lastname: Steiner
authors.affiliation: Department of Oral and Maxillofacial Surgery, Medical Faculty, RWTH Aachen University, Aachen, Germany.|Interdisciplinary Center for Laser Medicine, RWTH Aachen University, Aachen, Germany.
authors.forename: Frank
authors.initials: F
authors.lastname: Hölzle
authors.affiliation: Department of Dermatology and Allergology, RWTH Aachen University, Pauwelsstrasse 30, 52074, Aachen, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Skazik-Voogt
authors.affiliation: Department of Dermatology and Allergology, RWTH Aachen University, Pauwelsstrasse 30, 52074, Aachen, Germany.
authors.forename: Ruth
authors.initials: R
authors.lastname: Heise
authors.affiliation: Department of Dermatology and Allergology, RWTH Aachen University, Pauwelsstrasse 30, 52074, Aachen, Germany. JensMalte.Baron@post.rwth-aachen.de.|Interdisciplinary Center for Laser Medicine, RWTH Aachen University, Aachen, Germany. JensMalte.Baron@post.rwth-aachen.de.
authors.forename: Jens M
authors.initials: JM
authors.lastname: Baron
mesh_terms: D002921:Cicatrix / Q000473:pathology / Q000532:radiotherapy*; D000091344:Filaggrin Proteins; D015870:Gene Expression / Q000528:radiation effects; D005786:Gene Expression Regulation / Q000528:radiation effects; D006801:Humans; D053844:Lasers, Solid-State / Q000627:therapeutic use*; D028022:Low-Level Light Therapy / Q000379:methods; D008954:Models, Biological; D012867:Skin / Q000473:pathology / Q000528:radiation effects*; D046509:Tissue Culture Techniques
keywords: Full-thickness organotypic skin equivalents; Gene expression; Human skin reconstitution model; Laser and skin model