Low humidity altered the gene expression profile of keratinocytes in a three-dimensional skin model
Tóm tắt
The skin is constantly exposed to various external stimuli including humidity variations. Low humidity affects skin properties such as decreased water content of the stratum corneum, reduced skin elasticity, and itching. However, the effects of humidity on the skin cells are not completely understood. This study aimed to investigate how low humidity affects keratinocytes of the skin. In the present study, the effects of dry environment on the gene expression profile of epidermal keratinocytes were demonstrated using a three-dimensional skin model (3D-skin), composed of keratinocytes. Exposure of 3D-skin to low humidity (relative humidity ~ 10%) increased the expression levels of various genes, including those related to signal transduction and immune system. Accordingly, p38 mitogen-activated protein kinase (MAPK) signaling in keratinocytes of the 3D-skin was activated in response to low humidity for 30 min. Additionally, several chemokines, such as chemokine (C-X-C motif) ligand 1 (CXCL1) and Chemokine (C-C motif) ligand 20 (CCL20), were up regulated after 3 h of exposure to low humidity. We hypothesize that increased chemokine production may affect the immune system of the whole skin through chemoattractants. Our findings imply that keratinocytes sense low humidity and resultant activation of some cell-signaling pathways leads to variations in gene expression profiles including various chemokines. We provide evidence that keratinocytes adapt to external humidity variations.
Tài liệu tham khảo
citation_journal_title=Exp Dermatol; citation_title=The skin: an indispensable barrier; citation_author=E Proksch, JM Brandner, J-M Jensen; citation_volume=17; citation_publication_date=2008; citation_pages=1063-1072; citation_doi=10.1111/j.1600-0625.2008.00786.x; citation_id=CR1
citation_journal_title=J Investig Dermatol; citation_title=Stress-induced changes in skin barrier function in healthy women; citation_author=M Altemus, B Rao, FS Dhabhar, W Ding, RD Granstein; citation_volume=117; citation_publication_date=2001; citation_pages=309-317; citation_doi=10.1046/j.1523-1747.2001.01373.x; citation_id=CR2
citation_journal_title=Proc Natl Acad Sci; citation_title=Solar UV radiation reduces the barrier function of human skin; citation_author=K Biniek, K Levi, RH Dauskardt; citation_volume=109; citation_publication_date=2012; citation_pages=17111-17116; citation_doi=10.1073/pnas.1206851109; citation_id=CR3
citation_journal_title=Skin Res Technol; citation_title=Effect of exposure of human skin to a dry environment; citation_author=M Egawa, M Oguri, T Kuwahara, M Takahashi; citation_volume=8; citation_publication_date=2002; citation_pages=212-218; citation_doi=10.1034/j.1600-0846.2002.00351.x; citation_id=CR4
citation_journal_title=Arch Dermatol Res; citation_title=Transepidermal water loss and skin capacitance alterations among workers in an ultra-low humidity environment; citation_author=T-C Chou, K-H Lin, S-M Wang; citation_volume=296; citation_publication_date=2005; citation_pages=489-495; citation_doi=10.1007/s00403-005-0541-4; citation_id=CR5
citation_journal_title=Int Arch Occup Environ Health; citation_title=Ocular, nasal, dermal and general symptoms among commercial airline crews; citation_author=null T L, K A, B.-G D, ; citation_volume=75; citation_publication_date=2002; citation_pages=475-483; citation_doi=10.1007/s00420-002-0330-8; citation_id=CR6
citation_journal_title=J Invest Dermatol; citation_title=Climatic factors are associated with childhood eczema prevalence in the United States; citation_author=JI Silverberg, J Hanifin, EL Simpson; citation_volume=133; citation_publication_date=2013; citation_pages=1752-1759; citation_doi=10.1038/jid.2013.19; citation_id=CR7
citation_journal_title=J Biol Chem; citation_title=Selectively reduced glycerol in skin of aquaporin-3-deficient mice may account for impaired skin hydration, elasticity, and barrier recovery; citation_author=M Hara, T Ma, AS Verkman; citation_volume=277; citation_publication_date=2002; citation_pages=46616-46621; citation_doi=10.1074/jbc.M209003200; citation_id=CR8
citation_journal_title=Arch Dermatol Res; citation_title=Loss of water from the stratum corneum induces epidermal DNA synthesis in hairless mice; citation_author=J Sato, M Denda, Y Ashida, J Koyama; citation_volume=290; citation_publication_date=1998; citation_pages=634-637; citation_doi=10.1007/s004030050364; citation_id=CR9
citation_journal_title=J Investig Dermatol; citation_title=Low humidity stimulates epidermal DNA synthesis and amplifies the hyperproliferative response to barrier disruption: implication for seasonal exacerbations of inflammatory dermatoses; citation_author=M Denda, J Sato, T Tsuchiya, PM Elias, KR Feingold; citation_volume=111; citation_publication_date=1998; citation_pages=873-878; citation_doi=10.1046/j.1523-1747.1998.00364.x; citation_id=CR10
citation_journal_title=J Investig Dermatol; citation_title=Exposure to a dry environment enhances epidermal permeability barrier function; citation_author=M Denda, J Sato, Y Masuda; citation_volume=111; citation_publication_date=1998; citation_pages=858-863; citation_doi=10.1046/j.1523-1747.1998.00333.x; citation_id=CR11
citation_journal_title=Contact Dermatitis; citation_title=Regulation of the cutaneous allergic reaction by humidity; citation_author=J Hosoi, T Hariya, M Denda, T Tsuchiya; citation_volume=42; citation_publication_date=2000; citation_pages=81-84; citation_doi=10.1034/j.1600-0536.2000.042002081.x; citation_id=CR12
citation_journal_title=Br J Dermatol; citation_title=Epidermal interleukin-1 alpha generation is amplified at low humidity: implications for the pathogenesis of inflammatory dermatoses; citation_author=Y Ashida, M Ogo, M Denda; citation_volume=144; citation_publication_date=2001; citation_pages=238-243; citation_doi=10.1046/j.1365-2133.2001.04007.x; citation_id=CR13
citation_journal_title=The Journal of Toxicological Sciences; citation_title=Assessment of human epidermal model LabCyte EPI-MODEL for in vitro skin irritation testing according to European Centre for the Validation of Alternative Methods (ECVAM)-validated protocol.; citation_author=M Katoh, F Hamajima, T Ogasawara, K Hata; citation_volume=34; citation_publication_date=2009; citation_pages=327-334; citation_doi=10.2131/jts.34.327; citation_id=CR14
citation_journal_title=Genome Biol; citation_title=Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2; citation_author=MI Love, W Huber, S Anders; citation_publication_date=2014; citation_doi=10.1186/s13059-014-0550-8; citation_id=CR15
citation_journal_title=Bone Marrow Transplant; citation_title=Investigation of the freely available easy-to-use software ‘EZR’ for medical statistics; citation_author=Y Kanda; citation_volume=48; citation_publication_date=2013; citation_pages=452-458; citation_doi=10.1038/bmt.2012.244; citation_id=CR16
citation_journal_title=Nucleic Acids Res; citation_title=KEGG for linking genomes to life and the environment; citation_author=M Kanehisa, M Araki, S Goto; citation_volume=36; citation_publication_date=2007; citation_pages=D480-D484; citation_doi=10.1093/nar/gkm882; citation_id=CR17
citation_journal_title=Genes; citation_title=The role of mitogen-activated protein kinase-activated protein kinases (MAPKAPKs) in inflammation; citation_author=U Moens, S Kostenko, B Sveinbjørnsson; citation_volume=4; citation_publication_date=2013; citation_pages=101-133; citation_doi=10.3390/genes4020101; citation_id=CR18
citation_journal_title=Dev Cell; citation_title=TSC1 activates TGF-β-Smad2/3 signaling in growth arrest and epithelial-to-mesenchymal transition; citation_author=A Thien, MT Prentzell; citation_volume=32; citation_publication_date=2015; citation_pages=617-630; citation_doi=10.1016/j.devcel.2015.01.026; citation_id=CR19
citation_journal_title= Einstein (Sao Paulo); citation_title=Chemokines and immunity; citation_author=DC Palomino, LC Marti; citation_volume=13; citation_publication_date=2015; citation_pages=469-473; citation_doi=10.1590/S1679-45082015RB3438; citation_id=CR20
citation_journal_title=J Dermatol Sci; citation_title=Chemokine receptors in the pathogenesis and therapy of psoriasis; citation_author=T Mabuchi, TW Chang, S Quinter, ST Hwang; citation_volume=65; citation_publication_date=2012; citation_pages=4-11; citation_doi=10.1016/j.jdermsci.2011.11.007; citation_id=CR21
citation_journal_title=Blood; citation_title=CCR6/CCR10-mediated plasmacytoid dendritic cell recruitment to inflamed epithelia after instruction in lymphoid tissues; citation_author=V Sisirak, N Vey, B Vanbervliet; citation_volume=118; citation_publication_date=2011; citation_pages=5130-5140; citation_doi=10.1182/blood-2010-07-295626; citation_id=CR22
citation_journal_title=Cold Spring Harbor Perspect Biol; citation_title=The chemokine system in innate immunity; citation_author=CL Sokol, AD Luster; citation_volume=7; citation_publication_date=2015; citation_pages=a016303; citation_doi=10.1101/cshperspect.a016303; citation_id=CR23
citation_journal_title=Gastroenterology; citation_title=CXCL10 and CCL21 promote migration of pancreatic cancer cells toward sensory neurons and neural remodeling in tumors in mice, associated with pain in patients; citation_author=M Hirth, J Gandla, C Höper; citation_volume=159; citation_publication_date=2020; citation_pages=665-681.e613; citation_doi=10.1053/j.gastro.2020.04.037; citation_id=CR24
citation_journal_title=Int J Mol Sci; citation_title=The CCL20-CCR6 axis in cancer progression; citation_author=S Kadomoto, K Izumi, A Mizokami; citation_volume=21; citation_publication_date=2020; citation_pages=5186; citation_doi=10.3390/ijms21155186; citation_id=CR25
citation_journal_title=Nat Rev Immunol; citation_title=Exploring the full spectrum of macrophage activation; citation_author=DM Mosser, JP Edwards; citation_volume=8; citation_publication_date=2008; citation_pages=958-969; citation_doi=10.1038/nri2448; citation_id=CR26
citation_journal_title=Front Immunol; citation_title=Mechanisms of inflammation in neutrophil-mediated skin diseases; citation_author=AV Marzano, AG Ortega-Loayza, M Heath, D Morse, G Genovese, M Cugno; citation_volume=10; citation_publication_date=2019; citation_pages=1059; citation_doi=10.3389/fimmu.2019.01059; citation_id=CR27
citation_journal_title=FEBS J; citation_title=A guide to chemokines and their receptors; citation_author=CE Hughes, RJB Nibbs; citation_volume=285; citation_publication_date=2018; citation_pages=2944-2971; citation_doi=10.1111/febs.14466; citation_id=CR28
citation_journal_title= Immunity; citation_title=Chemokines; citation_author=A Zlotnik, O Yoshie; citation_volume=12; citation_publication_date=2000; citation_pages=121-127; citation_doi=10.1016/s1074-7613(00)80165-x; citation_id=CR29
citation_journal_title=Blood; citation_title=Mast cell and macrophage chemokines CXCL1/CXCL2 control the early stage of neutrophil recruitment during tissue inflammation; citation_author=K Filippo, A Dudeck, M Hasenberg; citation_volume=121; citation_publication_date=2013; citation_pages=4930-4937; citation_doi=10.1182/blood-2013-02-486217; citation_id=CR30
citation_journal_title=Cell Signal; citation_title=How do chemokines navigate neutrophils to the target site: dissecting the structural mechanisms and signaling pathways; citation_author=K Rajarathnam, M Schnoor, RM Richardson, S Rajagopal; citation_volume=54; citation_publication_date=2019; citation_pages=69-80; citation_doi=10.1016/j.cellsig.2018.11.004; citation_id=CR31
citation_journal_title=Int J Mol Sci; citation_title=CC chemokines in a tumor: a review of Pro-Cancer and anti-cancer properties of the ligands of receptors CCR1, CCR2, CCR3, and CCR4; citation_author=J Korbecki, K Kojder, D Siminska; citation_publication_date=2020; citation_doi=10.3390/ijms21218412; citation_id=CR32
citation_journal_title=Cell; citation_title=Mapping systemic inflammation and antibody responses in multisystem inflammatory syndrome in children (MIS-C); citation_author=CN Gruber, RS Patel, R Trachtman; citation_volume=183; citation_issue=982–995; citation_publication_date=2020; citation_doi=10.1016/j.cell.2020.09.034; citation_id=CR33
citation_journal_title=Arch Dermatol Res; citation_title=The effect of glycerol and humidity on desmosome degradation in stratum corneum; citation_author=A Rawlings, C Harding, A Watkinson, J Banks, C Ackerman, R Sabin; citation_volume=287; citation_publication_date=1995; citation_pages=457-464; citation_doi=10.1007/BF00373429; citation_id=CR34
citation_journal_title=J Dermatol Sci; citation_title=Dry condition affects desquamation of stratum corneum in vivo; citation_author=J Sato, M Denda, J Nakanishi, J Koyama; citation_volume=18; citation_publication_date=1998; citation_pages=163-169; citation_doi=10.1016/s0923-1811(98)00037-1; citation_id=CR35
citation_journal_title=Br J Dermatol; citation_title=Dry environment increases mast cell number and histamine content in dermis in hairless mice; citation_author=Y Ashida, M Denda; citation_volume=149; citation_publication_date=2003; citation_pages=240-247; citation_doi=10.1046/j.1365-2133.2003.05408.x; citation_id=CR36