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Erschienen in: Lasers in Medical Science 3/2016

01.04.2016 | Original Article

Effects of non-ablative fractional erbium glass laser treatment on gene regulation in human three-dimensional skin models

verfasst von: Philipp M. Amann, Yvonne Marquardt, Timm Steiner, Frank Hölzle, Claudia Skazik-Voogt, Ruth Heise, Jens M. Baron

Erschienen in: Lasers in Medical Science | Ausgabe 3/2016

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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.
Literatur
1.
Zurück zum Zitat Neis MM, Wendel A, Wiederholt T, Marquardt Y, Joussen S, Baron JM, Merk HF (2010) Expression and induction of cytochrome p450 isoenzymes in human skin equivalents. Skin Pharmacol Physiol 23(1):29–39CrossRefPubMed Neis MM, Wendel A, Wiederholt T, Marquardt Y, Joussen S, Baron JM, Merk HF (2010) Expression and induction of cytochrome p450 isoenzymes in human skin equivalents. Skin Pharmacol Physiol 23(1):29–39CrossRefPubMed
2.
Zurück zum Zitat Cornelissen C, Marquardt Y, Czaja K, Wenzel J, Frank J, Luscher-Firzlaff J, Luscher B, Baron JM (2012) IL-31 regulates differentiation and filaggrin expression in human organotypic skin models. J Allergy Clin Immunol 129(2):426–433, 433 e421-428CrossRefPubMed Cornelissen C, Marquardt Y, Czaja K, Wenzel J, Frank J, Luscher-Firzlaff J, Luscher B, Baron JM (2012) IL-31 regulates differentiation and filaggrin expression in human organotypic skin models. J Allergy Clin Immunol 129(2):426–433, 433 e421-428CrossRefPubMed
3.
Zurück zum Zitat Astashkina A, Grainger DW (2014) Critical analysis of 3-D organoid in vitro cell culture models for high-throughput drug candidate toxicity assessments. Adv Drug Deliv Rev 69–70:1–18CrossRefPubMed Astashkina A, Grainger DW (2014) Critical analysis of 3-D organoid in vitro cell culture models for high-throughput drug candidate toxicity assessments. Adv Drug Deliv Rev 69–70:1–18CrossRefPubMed
4.
Zurück zum Zitat Mathes SH, Ruffner H, Graf-Hausner U (2014) The use of skin models in drug development. Adv Drug Deliv Rev 69–70:81–102CrossRefPubMed Mathes SH, Ruffner H, Graf-Hausner U (2014) The use of skin models in drug development. Adv Drug Deliv Rev 69–70:81–102CrossRefPubMed
6.
Zurück zum Zitat Marquardt Y, Amann PM, Heise R, Czaja K, Steiner T, Merk HF, Skazik-Voogt C, Baron JM (2015) Characterization of a novel standardized human three-dimensional skin wound healing model using non-sequential fractional ultrapulsed CO2 laser treatments. Lasers Surg Med 47(3):257–265CrossRefPubMed Marquardt Y, Amann PM, Heise R, Czaja K, Steiner T, Merk HF, Skazik-Voogt C, Baron JM (2015) Characterization of a novel standardized human three-dimensional skin wound healing model using non-sequential fractional ultrapulsed CO2 laser treatments. Lasers Surg Med 47(3):257–265CrossRefPubMed
7.
Zurück zum Zitat Sardana K, Manjhi M, Garg VK, Sagar V (2014) Which type of atrophic acne scar (ice-pick, boxcar, or rolling) responds to nonablative fractional laser therapy? Dermatol Surg 40(3):288–300CrossRefPubMed Sardana K, Manjhi M, Garg VK, Sagar V (2014) Which type of atrophic acne scar (ice-pick, boxcar, or rolling) responds to nonablative fractional laser therapy? Dermatol Surg 40(3):288–300CrossRefPubMed
8.
Zurück zum Zitat Cho SB, Lee SJ, Cho S, Oh SH, Chung WS, Kang JM, Kim YK, Kim DH (2010) Non-ablative 1550-nm erbium-glass and ablative 10 600-nm carbon dioxide fractional lasers for acne scars: a randomized split-face study with blinded response evaluation. J Eur Acad Dermatol Venereol 24(8):921–925CrossRefPubMed Cho SB, Lee SJ, Cho S, Oh SH, Chung WS, Kang JM, Kim YK, Kim DH (2010) Non-ablative 1550-nm erbium-glass and ablative 10 600-nm carbon dioxide fractional lasers for acne scars: a randomized split-face study with blinded response evaluation. J Eur Acad Dermatol Venereol 24(8):921–925CrossRefPubMed
9.
Zurück zum Zitat Taudorf EH, Danielsen PL, Paulsen IF, Togsverd-Bo K, Dierickx C, Paasch U, Haedersdal M (2015) Non-ablative fractional laser provides long-term improvement of mature burn scars—a randomized controlled trial with histological assessment. Lasers Surg Med 47(2):141–147CrossRefPubMed Taudorf EH, Danielsen PL, Paulsen IF, Togsverd-Bo K, Dierickx C, Paasch U, Haedersdal M (2015) Non-ablative fractional laser provides long-term improvement of mature burn scars—a randomized controlled trial with histological assessment. Lasers Surg Med 47(2):141–147CrossRefPubMed
10.
Zurück zum Zitat Guimaraes PA, Haddad A, Sabino Neto M, Lage FC, Ferreira LM (2013) Striae distensae after breast augmentation: treatment using the nonablative fractionated 1550-nm erbium glass laser. Plast Reconstr Surg 131(3):636–642CrossRefPubMed Guimaraes PA, Haddad A, Sabino Neto M, Lage FC, Ferreira LM (2013) Striae distensae after breast augmentation: treatment using the nonablative fractionated 1550-nm erbium glass laser. Plast Reconstr Surg 131(3):636–642CrossRefPubMed
11.
Zurück zum Zitat Puri N (2013) A study on fractional erbium glass laser therapy versus chemical peeling for the treatment of melasma in female patients. J Cutan Aesthet Surg 6(3):148–151CrossRefPubMedPubMedCentral Puri N (2013) A study on fractional erbium glass laser therapy versus chemical peeling for the treatment of melasma in female patients. J Cutan Aesthet Surg 6(3):148–151CrossRefPubMedPubMedCentral
12.
Zurück zum Zitat Lee GY, Lee SJ, Kim WS (2011) The effect of a 1550 nm fractional erbium-glass laser in female pattern hair loss. J Eur Acad Dermatol Venereol 25(12):1450–1454CrossRefPubMed Lee GY, Lee SJ, Kim WS (2011) The effect of a 1550 nm fractional erbium-glass laser in female pattern hair loss. J Eur Acad Dermatol Venereol 25(12):1450–1454CrossRefPubMed
13.
Zurück zum Zitat Moneib H, Tawfik AA, Youssef SS, Fawzy MM (2014) Randomized split-face controlled study to evaluate 1550-nm fractionated erbium glass laser for treatment of acne vulgaris—an image analysis evaluation. Dermatol Surg 40(11):1191–1200CrossRefPubMed Moneib H, Tawfik AA, Youssef SS, Fawzy MM (2014) Randomized split-face controlled study to evaluate 1550-nm fractionated erbium glass laser for treatment of acne vulgaris—an image analysis evaluation. Dermatol Surg 40(11):1191–1200CrossRefPubMed
16.
Zurück zum Zitat Heise R, Skazik C, Marquardt Y, Czaja K, Sebastian K, Kurschat P, Gan L, Denecke B, Ekanayake-Bohlig S, Wilhelm KP, Merk HF, Baron JM (2012) Dexpanthenol modulates gene expression in skin wound healing in vivo. Skin Pharmacol Physiol 25(5):241–248CrossRefPubMed Heise R, Skazik C, Marquardt Y, Czaja K, Sebastian K, Kurschat P, Gan L, Denecke B, Ekanayake-Bohlig S, Wilhelm KP, Merk HF, Baron JM (2012) Dexpanthenol modulates gene expression in skin wound healing in vivo. Skin Pharmacol Physiol 25(5):241–248CrossRefPubMed
17.
Zurück zum Zitat Eckhart L, Declercq W, Ban J, Rendl M, Lengauer B, Mayer C, Lippens S, Vandenabeele P, Tschachler E (2000) Terminal differentiation of human keratinocytes and stratum corneum formation is associated with caspase-14 activation. J Invest Dermatol 115(6):1148–1151CrossRefPubMed Eckhart L, Declercq W, Ban J, Rendl M, Lengauer B, Mayer C, Lippens S, Vandenabeele P, Tschachler E (2000) Terminal differentiation of human keratinocytes and stratum corneum formation is associated with caspase-14 activation. J Invest Dermatol 115(6):1148–1151CrossRefPubMed
18.
Zurück zum Zitat Xu LY, Kilmer SL, Ross EV, Avram MM (2015) Bacterial infections following non-ablative fractional laser treatment: a case series and discussion. Lasers Surg Med 47(2):128–132CrossRefPubMed Xu LY, Kilmer SL, Ross EV, Avram MM (2015) Bacterial infections following non-ablative fractional laser treatment: a case series and discussion. Lasers Surg Med 47(2):128–132CrossRefPubMed
19.
Zurück zum Zitat Wang CC, Huang CL, Lee SC, Sue YM, Leu FJ (2013) Treatment of cosmetic tattoos with nonablative fractional laser in an animal model: a novel method with histopathologic evidence. Lasers Surg Med 45(2):116–122CrossRefPubMed Wang CC, Huang CL, Lee SC, Sue YM, Leu FJ (2013) Treatment of cosmetic tattoos with nonablative fractional laser in an animal model: a novel method with histopathologic evidence. Lasers Surg Med 45(2):116–122CrossRefPubMed
20.
Zurück zum Zitat Farkas JP, Richardson JA, Hoopman J, Brown SA, Kenkel JM (2009) Micro-island damage with a nonablative 1540-nm Er: glass fractional laser device in human skin. J Cosmet Dermatol 8(2):119–126CrossRefPubMed Farkas JP, Richardson JA, Hoopman J, Brown SA, Kenkel JM (2009) Micro-island damage with a nonablative 1540-nm Er: glass fractional laser device in human skin. J Cosmet Dermatol 8(2):119–126CrossRefPubMed
21.
Zurück zum Zitat Danso MO, van Drongelen V, Mulder A, van Esch J, Scott H, van Smeden J, El Ghalbzouri A, Bouwstra JA (2014) TNF-alpha and Th2 cytokines induce atopic dermatitis-like features on epidermal differentiation proteins and stratum corneum lipids in human skin equivalents. J Invest Dermatol 134(7):1941–1950CrossRefPubMed Danso MO, van Drongelen V, Mulder A, van Esch J, Scott H, van Smeden J, El Ghalbzouri A, Bouwstra JA (2014) TNF-alpha and Th2 cytokines induce atopic dermatitis-like features on epidermal differentiation proteins and stratum corneum lipids in human skin equivalents. J Invest Dermatol 134(7):1941–1950CrossRefPubMed
22.
Zurück zum Zitat Wang J, Hori K, Ding J, Huang Y, Kwan P, Ladak A, Tredget EE (2011) Toll-like receptors expressed by dermal fibroblasts contribute to hypertrophic scarring. J Cell Physiol 226(5):1265–1273CrossRefPubMed Wang J, Hori K, Ding J, Huang Y, Kwan P, Ladak A, Tredget EE (2011) Toll-like receptors expressed by dermal fibroblasts contribute to hypertrophic scarring. J Cell Physiol 226(5):1265–1273CrossRefPubMed
23.
Zurück zum Zitat Mofikoya BO, Adeyemo WL, Ugburo AO (2012) An overview of biological basis of pathologic scarring. Niger Postgrad Med J 19(1):40–45PubMed Mofikoya BO, Adeyemo WL, Ugburo AO (2012) An overview of biological basis of pathologic scarring. Niger Postgrad Med J 19(1):40–45PubMed
24.
Zurück zum Zitat Orringer JS, Rittie L, Baker D, Voorhees JJ, Fisher G (2010) Molecular mechanisms of nonablative fractionated laser resurfacing. Br J Dermatol 163(4):757–768CrossRefPubMed Orringer JS, Rittie L, Baker D, Voorhees JJ, Fisher G (2010) Molecular mechanisms of nonablative fractionated laser resurfacing. Br J Dermatol 163(4):757–768CrossRefPubMed
25.
Zurück zum Zitat Helbig D, Paasch U (2011) Molecular changes during skin aging and wound healing after fractional ablative photothermolysis. Skin Res Technol 17(1):119–128CrossRefPubMed Helbig D, Paasch U (2011) Molecular changes during skin aging and wound healing after fractional ablative photothermolysis. Skin Res Technol 17(1):119–128CrossRefPubMed
27.
28.
Zurück zum Zitat Fujiwara M, Muragaki Y, Ooshima A (2005) Keloid-derived fibroblasts show increased secretion of factors involved in collagen turnover and depend on matrix metalloproteinase for migration. Br J Dermatol 153(2):295–300CrossRefPubMed Fujiwara M, Muragaki Y, Ooshima A (2005) Keloid-derived fibroblasts show increased secretion of factors involved in collagen turnover and depend on matrix metalloproteinase for migration. Br J Dermatol 153(2):295–300CrossRefPubMed
29.
Zurück zum Zitat Tsou R, Cole JK, Nathens AB, Isik FF, Heimbach DM, Engrav LH, Gibran NS (2000) Analysis of hypertrophic and normal scar gene expression with cDNA microarrays. J Burn Care Rehabil 21(6):541–550CrossRefPubMed Tsou R, Cole JK, Nathens AB, Isik FF, Heimbach DM, Engrav LH, Gibran NS (2000) Analysis of hypertrophic and normal scar gene expression with cDNA microarrays. J Burn Care Rehabil 21(6):541–550CrossRefPubMed
30.
Zurück zum Zitat Wang Q, Dong Y, Geng S, Su H, Ge W, Zhen C (2014) Photodynamic therapy inhibits the formation of hypertrophic scars in rabbit ears by regulating metalloproteinases and tissue inhibitor of metalloproteinase-1. Clin Exp Dermatol 39(2):196–201CrossRefPubMed Wang Q, Dong Y, Geng S, Su H, Ge W, Zhen C (2014) Photodynamic therapy inhibits the formation of hypertrophic scars in rabbit ears by regulating metalloproteinases and tissue inhibitor of metalloproteinase-1. Clin Exp Dermatol 39(2):196–201CrossRefPubMed
31.
Zurück zum Zitat Reno F, Grazianetti P, Stella M, Magliacani G, Pezzuto C, Cannas M (2002) Release and activation of matrix metalloproteinase-9 during in vitro mechanical compression in hypertrophic scars. Arch Dermatol 138(4):475–478CrossRefPubMed Reno F, Grazianetti P, Stella M, Magliacani G, Pezzuto C, Cannas M (2002) Release and activation of matrix metalloproteinase-9 during in vitro mechanical compression in hypertrophic scars. Arch Dermatol 138(4):475–478CrossRefPubMed
32.
Zurück zum Zitat Qu L, Liu A, Zhou L, He C, Grossman PH, Moy RL, Mi QS, Ozog D (2012) Clinical and molecular effects on mature burn scars after treatment with a fractional CO(2) laser. Lasers Surg Med 44(7):517–524CrossRefPubMed Qu L, Liu A, Zhou L, He C, Grossman PH, Moy RL, Mi QS, Ozog D (2012) Clinical and molecular effects on mature burn scars after treatment with a fractional CO(2) laser. Lasers Surg Med 44(7):517–524CrossRefPubMed
33.
Zurück zum Zitat Ozog DM, Liu A, Chaffins ML, Ormsby AH, Fincher EF, Chipps LK, Mi QS, Grossman PH, Pui JC, Moy RL (2013) Evaluation of clinical results, histological architecture, and collagen expression following treatment of mature burn scars with a fractional carbon dioxide laser. JAMA Dermatol 149(1):50–57CrossRefPubMed Ozog DM, Liu A, Chaffins ML, Ormsby AH, Fincher EF, Chipps LK, Mi QS, Grossman PH, Pui JC, Moy RL (2013) Evaluation of clinical results, histological architecture, and collagen expression following treatment of mature burn scars with a fractional carbon dioxide laser. JAMA Dermatol 149(1):50–57CrossRefPubMed
34.
Zurück zum Zitat Bullard KM, Mudgett J, Scheuenstuhl H, Hunt TK, Banda MJ (1999) Stromelysin-1-deficient fibroblasts display impaired contraction in vitro. J Surg Res 84(1):31–34CrossRefPubMed Bullard KM, Mudgett J, Scheuenstuhl H, Hunt TK, Banda MJ (1999) Stromelysin-1-deficient fibroblasts display impaired contraction in vitro. J Surg Res 84(1):31–34CrossRefPubMed
35.
Zurück zum Zitat Melerzanov A, Lavrov A, Sakania L, Korsunskaya I, Petersen E, Sobelev V (2014) Effects of laser radiation on MMP gene expression in keratinocytes. PRIME J 4(3):39–44 Melerzanov A, Lavrov A, Sakania L, Korsunskaya I, Petersen E, Sobelev V (2014) Effects of laser radiation on MMP gene expression in keratinocytes. PRIME J 4(3):39–44
Metadaten
Titel
Effects of non-ablative fractional erbium glass laser treatment on gene regulation in human three-dimensional skin models
verfasst von
Philipp M. Amann
Yvonne Marquardt
Timm Steiner
Frank Hölzle
Claudia Skazik-Voogt
Ruth Heise
Jens M. Baron
Publikationsdatum
01.04.2016
Verlag
Springer London
Erschienen in
Lasers in Medical Science / Ausgabe 3/2016
Print ISSN: 0268-8921
Elektronische ISSN: 1435-604X
DOI
https://doi.org/10.1007/s10103-015-1863-x

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