Dysregulation of Connexin Expression Plays a Pivotal Role in Psoriasis
Background: Psoriasis, a chronic inflammatory disease affecting 2–3% of the population, is characterised by epidermal hyperplasia, a sustained pro-inflammatory immune response and is primarily a T-cell driven disease. Previous work determined that Connexin26 is upregulated in psoriatic tissue. This...
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| Published in | International journal of molecular sciences Vol. 22; no. 11; p. 6060 |
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| Main Authors | , , , , , , |
| Format | Journal Article |
| Language | English |
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MDPI
04.06.2021
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| Online Access | Get full text |
| ISSN | 1422-0067 1422-0067 |
| DOI | 10.3390/ijms22116060 |
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| Abstract | Background: Psoriasis, a chronic inflammatory disease affecting 2–3% of the population, is characterised by epidermal hyperplasia, a sustained pro-inflammatory immune response and is primarily a T-cell driven disease. Previous work determined that Connexin26 is upregulated in psoriatic tissue. This study extends these findings. Methods: Biopsies spanning psoriatic plaque (PP) and non-involved tissue (PN) were compared to normal controls (NN). RNA was isolated and subject to real-time PCR to determine gene expression profiles, including GJB2/CX26, GJB6/CX30 and GJA1/CX43. Protein expression was assessed by immunohistochemistry. Keratinocytes and fibroblasts were isolated and used in 3D organotypic models. The pro-inflammatory status of fibroblasts and 3D cultures was assessed via ELISA and RnD cytokine arrays in the presence or absence of the connexin channel blocker Gap27. Results: Connexin26 expression is dramatically enhanced at both transcriptional and translational level in PP and PN tissue compared to NN (>100x). In contrast, CX43 gene expression is not affected, but the protein is post-translationally modified and accumulates in psoriatic tissue. Fibroblasts isolated from psoriatic patients had a higher inflammatory index than normal fibroblasts and drove normal keratinocytes to adopt a “psoriatic phenotype” in a 3D-organotypic model. Exposure of normal fibroblasts to the pro-inflammatory mediator peptidoglycan, isolated from Staphylococcus aureus enhanced cytokine release, an event protected by Gap27. Conclusion: dysregulation of the connexin26:43 expression profile in psoriatic tissue contributes to an imbalance of cellular events. Inhibition of connexin signalling reduces pro-inflammatory events and may hold therapeutic benefit. |
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| AbstractList | Background: Psoriasis, a chronic inflammatory disease affecting 2–3% of the population, is characterised by epidermal hyperplasia, a sustained pro-inflammatory immune response and is primarily a T-cell driven disease. Previous work determined that Connexin26 is upregulated in psoriatic tissue. This study extends these findings. Methods: Biopsies spanning psoriatic plaque (PP) and non-involved tissue (PN) were compared to normal controls (NN). RNA was isolated and subject to real-time PCR to determine gene expression profiles, including
GJB2/CX26
,
GJB6/CX30
and
GJA1/CX43
. Protein expression was assessed by immunohistochemistry. Keratinocytes and fibroblasts were isolated and used in 3D organotypic models. The pro-inflammatory status of fibroblasts and 3D cultures was assessed via ELISA and RnD cytokine arrays in the presence or absence of the connexin channel blocker Gap27. Results: Connexin26 expression is dramatically enhanced at both transcriptional and translational level in PP and PN tissue compared to NN (>100x). In contrast, CX43 gene expression is not affected, but the protein is post-translationally modified and accumulates in psoriatic tissue. Fibroblasts isolated from psoriatic patients had a higher inflammatory index than normal fibroblasts and drove normal keratinocytes to adopt a “psoriatic phenotype” in a 3D-organotypic model. Exposure of normal fibroblasts to the pro-inflammatory mediator peptidoglycan, isolated from
Staphylococcus aureus
enhanced cytokine release, an event protected by Gap27. Conclusion: dysregulation of the connexin26:43 expression profile in psoriatic tissue contributes to an imbalance of cellular events. Inhibition of connexin signalling reduces pro-inflammatory events and may hold therapeutic benefit. Background: Psoriasis, a chronic inflammatory disease affecting 2–3% of the population, is characterised by epidermal hyperplasia, a sustained pro-inflammatory immune response and is primarily a T-cell driven disease. Previous work determined that Connexin26 is upregulated in psoriatic tissue. This study extends these findings. Methods: Biopsies spanning psoriatic plaque (PP) and non-involved tissue (PN) were compared to normal controls (NN). RNA was isolated and subject to real-time PCR to determine gene expression profiles, including GJB2/CX26, GJB6/CX30 and GJA1/CX43. Protein expression was assessed by immunohistochemistry. Keratinocytes and fibroblasts were isolated and used in 3D organotypic models. The pro-inflammatory status of fibroblasts and 3D cultures was assessed via ELISA and RnD cytokine arrays in the presence or absence of the connexin channel blocker Gap27. Results: Connexin26 expression is dramatically enhanced at both transcriptional and translational level in PP and PN tissue compared to NN (>100x). In contrast, CX43 gene expression is not affected, but the protein is post-translationally modified and accumulates in psoriatic tissue. Fibroblasts isolated from psoriatic patients had a higher inflammatory index than normal fibroblasts and drove normal keratinocytes to adopt a “psoriatic phenotype” in a 3D-organotypic model. Exposure of normal fibroblasts to the pro-inflammatory mediator peptidoglycan, isolated from Staphylococcus aureus enhanced cytokine release, an event protected by Gap27. Conclusion: dysregulation of the connexin26:43 expression profile in psoriatic tissue contributes to an imbalance of cellular events. Inhibition of connexin signalling reduces pro-inflammatory events and may hold therapeutic benefit. Psoriasis, a chronic inflammatory disease affecting 2-3% of the population, is characterised by epidermal hyperplasia, a sustained pro-inflammatory immune response and is primarily a T-cell driven disease. Previous work determined that Connexin26 is upregulated in psoriatic tissue. This study extends these findings.BACKGROUNDPsoriasis, a chronic inflammatory disease affecting 2-3% of the population, is characterised by epidermal hyperplasia, a sustained pro-inflammatory immune response and is primarily a T-cell driven disease. Previous work determined that Connexin26 is upregulated in psoriatic tissue. This study extends these findings.Biopsies spanning psoriatic plaque (PP) and non-involved tissue (PN) were compared to normal controls (NN). RNA was isolated and subject to real-time PCR to determine gene expression profiles, including GJB2/CX26, GJB6/CX30 and GJA1/CX43. Protein expression was assessed by immunohistochemistry. Keratinocytes and fibroblasts were isolated and used in 3D organotypic models. The pro-inflammatory status of fibroblasts and 3D cultures was assessed via ELISA and RnD cytokine arrays in the presence or absence of the connexin channel blocker Gap27.METHODSBiopsies spanning psoriatic plaque (PP) and non-involved tissue (PN) were compared to normal controls (NN). RNA was isolated and subject to real-time PCR to determine gene expression profiles, including GJB2/CX26, GJB6/CX30 and GJA1/CX43. Protein expression was assessed by immunohistochemistry. Keratinocytes and fibroblasts were isolated and used in 3D organotypic models. The pro-inflammatory status of fibroblasts and 3D cultures was assessed via ELISA and RnD cytokine arrays in the presence or absence of the connexin channel blocker Gap27.Connexin26 expression is dramatically enhanced at both transcriptional and translational level in PP and PN tissue compared to NN (>100x). In contrast, CX43 gene expression is not affected, but the protein is post-translationally modified and accumulates in psoriatic tissue. Fibroblasts isolated from psoriatic patients had a higher inflammatory index than normal fibroblasts and drove normal keratinocytes to adopt a "psoriatic phenotype" in a 3D-organotypic model. Exposure of normal fibroblasts to the pro-inflammatory mediator peptidoglycan, isolated from Staphylococcus aureus enhanced cytokine release, an event protected by Gap27.RESULTSConnexin26 expression is dramatically enhanced at both transcriptional and translational level in PP and PN tissue compared to NN (>100x). In contrast, CX43 gene expression is not affected, but the protein is post-translationally modified and accumulates in psoriatic tissue. Fibroblasts isolated from psoriatic patients had a higher inflammatory index than normal fibroblasts and drove normal keratinocytes to adopt a "psoriatic phenotype" in a 3D-organotypic model. Exposure of normal fibroblasts to the pro-inflammatory mediator peptidoglycan, isolated from Staphylococcus aureus enhanced cytokine release, an event protected by Gap27.dysregulation of the connexin26:43 expression profile in psoriatic tissue contributes to an imbalance of cellular events. Inhibition of connexin signalling reduces pro-inflammatory events and may hold therapeutic benefit.CONCLUSIONdysregulation of the connexin26:43 expression profile in psoriatic tissue contributes to an imbalance of cellular events. Inhibition of connexin signalling reduces pro-inflammatory events and may hold therapeutic benefit. |
| Author | Garcia-Vega, Laura O’Shaughnessy, Erin M. Duffy, William Martin, Patricia E. Zamiri, Mozheh Burden, A. David Hussey, Keith |
| AuthorAffiliation | 4 Institute of Infection Immunity and Inflammation, University of Glasgow, Glasgow G12 8TA, UK; David.Burden@glasgow.ac.uk 1 Department of Biological and Biomedical Sciences, School of Health and Life Sciences, Glasgow Caledonian University, Glasgow G4 0BA, UK; erinoshaughnessy@rocketmail.com (E.M.O.); v.lauramaria.garcia@gmail.com (L.G.-V.) 2 Department of Dermatology, University Hospital Crosshouse, Kilmarnock KA2 0BE, UK; william.duffy2@aapct.scot.nhs.uk (W.D.); mozheh.zamiri@glasgow.ac.uk (M.Z.) 3 Department of Vascular Surgery, Queen Elizabeth University Hospital, Glasgow G51 4TF, UK; keithhussey79@hotmail.com 5 Department of Dermatology, Queen Elizabeth University Hospital, Glasgow G51 4TF, UK |
| AuthorAffiliation_xml | – name: 3 Department of Vascular Surgery, Queen Elizabeth University Hospital, Glasgow G51 4TF, UK; keithhussey79@hotmail.com – name: 1 Department of Biological and Biomedical Sciences, School of Health and Life Sciences, Glasgow Caledonian University, Glasgow G4 0BA, UK; erinoshaughnessy@rocketmail.com (E.M.O.); v.lauramaria.garcia@gmail.com (L.G.-V.) – name: 2 Department of Dermatology, University Hospital Crosshouse, Kilmarnock KA2 0BE, UK; william.duffy2@aapct.scot.nhs.uk (W.D.); mozheh.zamiri@glasgow.ac.uk (M.Z.) – name: 4 Institute of Infection Immunity and Inflammation, University of Glasgow, Glasgow G12 8TA, UK; David.Burden@glasgow.ac.uk – name: 5 Department of Dermatology, Queen Elizabeth University Hospital, Glasgow G51 4TF, UK |
| Author_xml | – sequence: 1 givenname: Erin M. surname: O’Shaughnessy fullname: O’Shaughnessy, Erin M. – sequence: 2 givenname: William surname: Duffy fullname: Duffy, William – sequence: 3 givenname: Laura surname: Garcia-Vega fullname: Garcia-Vega, Laura – sequence: 4 givenname: Keith surname: Hussey fullname: Hussey, Keith – sequence: 5 givenname: A. David surname: Burden fullname: Burden, A. David – sequence: 6 givenname: Mozheh surname: Zamiri fullname: Zamiri, Mozheh – sequence: 7 givenname: Patricia E. orcidid: 0000-0003-0890-8059 surname: Martin fullname: Martin, Patricia E. |
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| Cites_doi | 10.1083/jcb.106.3.761 10.1371/journal.pone.0186067 10.3390/biology10010059 10.1006/meth.2001.1262 10.1007/s13311-019-00786-5 10.1111/j.1600-0846.2007.00210.x 10.1172/JCI27186 10.1038/jid.2014.28 10.1096/fj.06-5828com 10.1684/ejd.2012.1649 10.1016/j.yexcr.2012.12.013 10.1002/eji.201948254 10.1046/j.1523-1747.1998.00248.x 10.1002/jcp.28206 10.3390/ijms19061778 10.1038/sj.jid.5701125 10.1007/s00441-014-2094-3 10.3390/cells8080807 10.1038/ng.690 10.1038/jid.2011.182 10.4103/1673-5374.290097 10.1089/ten.tea.2014.0651 10.1085/jgp.201711782 10.3390/ijms19020604 10.1007/s13346-020-00763-y 10.1016/j.jid.2015.11.017 10.1038/s41598-018-29472-w 10.1085/jgp.201812219 10.1016/j.jid.2018.12.019 10.3390/ijms19051354 10.1016/j.jid.2017.05.015 10.1016/j.clindermatol.2010.09.014 10.1046/j.1523-1747.1999.00512.x 10.1007/s00441-009-0848-0 10.1074/jbc.M402006200 10.1080/17460441.2020.1773787 10.1016/j.jid.2018.05.018 10.3390/ijms20246186 10.1111/bjd.15682 10.1111/tan.12595 10.1111/j.1582-4934.2010.01057.x 10.1186/s12864-016-3188-y 10.1016/j.celrep.2018.09.006 10.1002/adbi.201800227 10.1111/j.1600-0625.2009.01013.x 10.1016/j.clindermatol.2019.01.011 10.1002/adhm.201600175 10.1016/j.jid.2018.07.032 10.1016/j.febslet.2014.01.049 10.3390/ijms20061475 10.1080/02713683.2019.1584321 10.1002/kjm2.12034 10.1161/JAHA.118.011006 10.1042/BJ20091753 10.1111/j.1365-2133.1995.tb00720.x 10.1038/jid.2011.344 10.1242/jcs.03320 10.1038/sj.bjp.0706429 10.1016/j.clindermatol.2007.08.016 10.1038/nature12171 10.1186/1471-2105-13-S2-S11 10.1016/j.semcdb.2015.12.010 10.2340/00015555-2859 10.1038/s41467-019-12253-y 10.1080/10409238.2016.1204980 10.1046/j.1523-1747.2002.19505.x 10.1111/j.1600-0625.2012.01521.x 10.5826/dpc.0503a02 10.1002/jcp.22705 |
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| References | Livak (ref_69) 2001; 25 Denda (ref_50) 2002; 119 Yao (ref_32) 2015; 86 ref_14 Solan (ref_60) 2016; 50 Pollok (ref_29) 2011; 15 Donnelly (ref_16) 2012; 21 ref_11 Lewis (ref_3) 2019; 37 ref_10 ref_53 Djalilian (ref_36) 2006; 116 Ahn (ref_18) 2018; 8 Acosta (ref_12) 2021; 16 Matsuyoshi (ref_61) 1995; 132 Wright (ref_67) 2013; 319 ref_19 Labarthe (ref_7) 1998; 111 Garcia (ref_39) 2016; 136 Boukamp (ref_66) 1988; 106 Denda (ref_49) 2007; 13 Assarsson (ref_2) 2018; 98 Barrio (ref_48) 2006; 20 Tsutsumi (ref_38) 2009; 338 Fyhrquist (ref_6) 2019; 10 Ahn (ref_17) 2016; 17 ref_25 Nor (ref_46) 2020; 17 Killeen (ref_52) 2018; 138 ref_21 Shaker (ref_62) 2012; 22 Martin (ref_35) 2015; 360 Yang (ref_55) 2019; 44 Robertson (ref_15) 2010; 432 Calder (ref_56) 2015; 21 Lucke (ref_8) 1999; 112 Sun (ref_34) 2010; 42 Willebrords (ref_13) 2016; 51 Sagi (ref_63) 2011; 29 Gallo (ref_4) 2007; 25 Burnstock (ref_51) 2006; 147 Mori (ref_31) 2006; 119 Qiao (ref_64) 2019; 139 ref_30 Sezer (ref_24) 2015; 5 Caufriez (ref_43) 2020; 15 Leithe (ref_68) 2004; 279 Yang (ref_23) 2017; 137 Cheng (ref_42) 2018; 25 Dou (ref_20) 2017; 177 Solan (ref_26) 2014; 588 Lazzerini (ref_59) 2019; 8 Gallo (ref_5) 2011; 131 ref_47 Findley (ref_33) 2013; 498 Li (ref_9) 2014; 134 Chen (ref_22) 2019; 35 Wang (ref_37) 2009; 19 ref_44 Gilmartin (ref_57) 2016; 5 ref_1 Kandyba (ref_28) 2008; 128 Coutinho (ref_45) 2020; 10 Capuccino (ref_41) 2019; 151 Chen (ref_54) 2020; 50 Liang (ref_58) 2019; 139 Villanelo (ref_40) 2018; 150 Wright (ref_65) 2012; 227 Burnstock (ref_27) 2012; 132 |
| References_xml | – volume: 106 start-page: 761 year: 1988 ident: ref_66 article-title: Normal keratinization in a spontaneously immortalized aneuploid human keratinocyte cell line publication-title: J. Cell Biol. doi: 10.1083/jcb.106.3.761 – ident: ref_19 doi: 10.1371/journal.pone.0186067 – ident: ref_10 doi: 10.3390/biology10010059 – volume: 25 start-page: 402 year: 2001 ident: ref_69 article-title: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method publication-title: Methods doi: 10.1006/meth.2001.1262 – volume: 17 start-page: 371 year: 2020 ident: ref_46 article-title: Connexin Hemichannel Block Using Orally Delivered Tonabersat Improves Outcomes in Animal Models of Retinal Disease publication-title: Neurotherapeutics doi: 10.1007/s13311-019-00786-5 – volume: 13 start-page: 195 year: 2007 ident: ref_49 article-title: Air-exposed keratinocytes exhibited intracellular calcium oscillation publication-title: Ski. Res. Technol. doi: 10.1111/j.1600-0846.2007.00210.x – volume: 116 start-page: 1243 year: 2006 ident: ref_36 article-title: Connexin 26 regulates epidermal barrier and wound remodeling and promotes psoriasiform response publication-title: J. Clin. Investig. doi: 10.1172/JCI27186 – volume: 134 start-page: 1828 year: 2014 ident: ref_9 article-title: Transcriptome Analysis of Psoriasis in a Large Case–Control Sample: RNA-Seq Provides Insights into Disease Mechanisms publication-title: J. Investig. Dermatol. doi: 10.1038/jid.2014.28 – volume: 20 start-page: 2329 year: 2006 ident: ref_48 article-title: Species specificity of mammalian connexin-26 to form open voltage-gated hemichannels publication-title: FASEB J. doi: 10.1096/fj.06-5828com – volume: 22 start-page: 218 year: 2012 ident: ref_62 article-title: Connexin 26 in psoriatic skin before and after two conventional therapeutic modalities: Methotrexate and PUVA publication-title: Eur. J. Dermatol. doi: 10.1684/ejd.2012.1649 – volume: 319 start-page: 390 year: 2013 ident: ref_67 article-title: Cell motility in models of wounded human skin is improved by Gap27 despite raised glucose, insulin and IGFBP-5 publication-title: Exp. Cell Res. doi: 10.1016/j.yexcr.2012.12.013 – volume: 50 start-page: 170 year: 2020 ident: ref_54 article-title: Pannexin-1 promotes NLRP3 activation during apoptosis but is dispensable for canonical or noncanonical inflammasome activation publication-title: Eur. J. Immunol. doi: 10.1002/eji.201948254 – volume: 111 start-page: 72 year: 1998 ident: ref_7 article-title: Upregulation of Connexin 26 Between Keratinocytes of Psoriatic Lesions publication-title: J. Investig. Dermatol. doi: 10.1046/j.1523-1747.1998.00248.x – ident: ref_14 doi: 10.1002/jcp.28206 – ident: ref_47 doi: 10.3390/ijms19061778 – volume: 128 start-page: 1039 year: 2008 ident: ref_28 article-title: A Murine Living Skin Equivalent Amenable to Live-Cell Imaging: Analysis of the Roles of Connexins in the Epidermis publication-title: J. Investig. Dermatol. doi: 10.1038/sj.jid.5701125 – volume: 360 start-page: 645 year: 2015 ident: ref_35 article-title: Connexins and skin disease: Insights into the role of beta connexins in skin homeostasis publication-title: Cell Tissue Res. doi: 10.1007/s00441-014-2094-3 – ident: ref_21 doi: 10.3390/cells8080807 – volume: 42 start-page: 1005 year: 2010 ident: ref_34 article-title: Association analyses identify six new psoriasis susceptibility loci in the Chinese population publication-title: Nat. Genet. doi: 10.1038/ng.690 – volume: 131 start-page: 1974 year: 2011 ident: ref_5 article-title: Microbial Symbiosis with the Innate Immune Defense System of the Skin publication-title: J. Investig. Dermatol. doi: 10.1038/jid.2011.182 – volume: 16 start-page: 482 year: 2021 ident: ref_12 article-title: Connexin therapeutics: Blocking connexin hemichannel pores is distinct from blocking pannexin channels or gap junctions publication-title: Neural Regen. Res. doi: 10.4103/1673-5374.290097 – volume: 21 start-page: 1752 year: 2015 ident: ref_56 article-title: Inhibition of Connexin 43 Hemichannel-Mediated ATP Release Attenuates Early Inflammation During the Foreign Body Response publication-title: Tissue Eng. Part A doi: 10.1089/ten.tea.2014.0651 – volume: 150 start-page: 697 year: 2018 ident: ref_40 article-title: The syndromic deafness mutation G12R impairs fast and slow gating in Cx26 hemichannels publication-title: J. Gen. Physiol. doi: 10.1085/jgp.201711782 – ident: ref_30 doi: 10.3390/ijms19020604 – volume: 10 start-page: 751 year: 2020 ident: ref_45 article-title: Xentry-Gap19 inhibits Connexin43 hemichannel opening especially during hypoxic injury publication-title: Drug Deliv. Transl. Res. doi: 10.1007/s13346-020-00763-y – volume: 136 start-page: 574 year: 2016 ident: ref_39 article-title: From Hyperactive Connexin26 Hemichannels to Impairments in Epidermal Calcium Gradient and Permeability Barrier in the Keratitis-Ichthyosis-Deafness Syndrome publication-title: J. Investig. Dermatol. doi: 10.1016/j.jid.2015.11.017 – volume: 8 start-page: 1 year: 2018 ident: ref_18 article-title: RNA-seq and flow-cytometry of conventional, scalp, and palmoplantar psoriasis reveal shared and distinct molecular pathways publication-title: Sci. Rep. doi: 10.1038/s41598-018-29472-w – volume: 151 start-page: 328 year: 2019 ident: ref_41 article-title: The connexin26 human mutation N14K disrupts cytosolic intersubunit interactions and promotes channel opening publication-title: J. Gen. Physiol. doi: 10.1085/jgp.201812219 – volume: 139 start-page: 1470 year: 2019 ident: ref_64 article-title: Mechanical Stretch Exacerbates Psoriasis by Stimulating Keratinocyte Proliferation and Cytokine Production publication-title: J. Investig. Dermatol. doi: 10.1016/j.jid.2018.12.019 – ident: ref_11 doi: 10.3390/ijms19051354 – volume: 137 start-page: 2168 year: 2017 ident: ref_23 article-title: Nrf2 Promotes Keratinocyte Proliferation in Psoriasis through Up-Regulation of Keratin 6, Keratin 16, and Keratin 17 publication-title: J. Investig. Dermatol. doi: 10.1016/j.jid.2017.05.015 – volume: 29 start-page: 231 year: 2011 ident: ref_63 article-title: The Koebner phenomenon publication-title: Clin. Dermatol. doi: 10.1016/j.clindermatol.2010.09.014 – volume: 112 start-page: 354 year: 1999 ident: ref_8 article-title: Upregulation of Connexin 26 is a Feature of Keratinocyte Differentiation in Hyperproliferative Epidermis, Vaginal Epithelium, and Buccal Epithelium publication-title: J. Investig. Dermatol. doi: 10.1046/j.1523-1747.1999.00512.x – volume: 338 start-page: 99 year: 2009 ident: ref_38 article-title: Mechanical-stimulation-evoked calcium waves in proliferating and differentiated human keratinocytes publication-title: Cell Tissue Res. doi: 10.1007/s00441-009-0848-0 – volume: 279 start-page: 50089 year: 2004 ident: ref_68 article-title: Ubiquitination and Down-regulation of Gap Junction Protein Connexin-43 in Response to 12-O-Tetradecanoylphorbol 13-Acetate Treatment publication-title: J. Biol. Chem. doi: 10.1074/jbc.M402006200 – volume: 15 start-page: 1213 year: 2020 ident: ref_43 article-title: Peptide-based targeting of connexins and pannexins for therapeutic purposes publication-title: Expert Opin. Drug Discov. doi: 10.1080/17460441.2020.1773787 – volume: 138 start-page: 2595 year: 2018 ident: ref_52 article-title: Extracellular ATP and IL-23 Form a Local Inflammatory Circuit Leading to the Development of a Neutrophil-Dependent Psoriasiform Dermatitis publication-title: J. Investig. Dermatol. doi: 10.1016/j.jid.2018.05.018 – ident: ref_44 doi: 10.3390/ijms20246186 – volume: 177 start-page: 1349 year: 2017 ident: ref_20 article-title: Integrative analyses reveal biological pathways and key genes in psoriasis publication-title: Br. J. Dermatol. doi: 10.1111/bjd.15682 – volume: 86 start-page: 134 year: 2015 ident: ref_32 article-title: A genetic coding variant rs72474224 in GJB2 is associated with clinical features of psoriasis vulgaris in a Chinese Han population publication-title: Tissue Antigens doi: 10.1111/tan.12595 – volume: 15 start-page: 861 year: 2011 ident: ref_29 article-title: Connexin 43 mimetic peptide Gap27 reveals potential differences in the role of Cx43 in wound repair between diabetic and non-diabetic cells publication-title: J. Cell. Mol. Med. doi: 10.1111/j.1582-4934.2010.01057.x – volume: 17 start-page: 1 year: 2016 ident: ref_17 article-title: Network analysis of psoriasis reveals biological pathways and roles for coding and long non-coding RNAs publication-title: BMC Genom. doi: 10.1186/s12864-016-3188-y – volume: 25 start-page: 871 year: 2018 ident: ref_42 article-title: Transcriptional Programming of Normal and Inflamed Human Epidermis at Single-Cell Resolution publication-title: Cell Rep. doi: 10.1016/j.celrep.2018.09.006 – ident: ref_53 doi: 10.1002/adbi.201800227 – volume: 19 start-page: 633 year: 2009 ident: ref_37 article-title: Overexpression of connexin26 in the basal keratinocytes reduces sensitivity to tumor promoter TPA publication-title: Exp. Dermatol. doi: 10.1111/j.1600-0625.2009.01013.x – volume: 37 start-page: 160 year: 2019 ident: ref_3 article-title: Mechanisms of microbial pathogenesis and the role of the skin mi-crobiome in psoriasis: A review publication-title: Clin. Dermatol. doi: 10.1016/j.clindermatol.2019.01.011 – volume: 5 start-page: 1786 year: 2016 ident: ref_57 article-title: Sustained Release of Cx43 Antisense Oligodeoxynucleotides from Coated Collagen Scaffolds Promotes Wound Healing publication-title: Adv. Healthc. Mater. doi: 10.1002/adhm.201600175 – volume: 139 start-page: 400 year: 2019 ident: ref_58 article-title: IL-22 Down-Regulates Cx43 Expression and Decreases Gap Junctional Intercellular Communication by Activating the JNK Pathway in Psoriasis publication-title: J. Investig. Dermatol. doi: 10.1016/j.jid.2018.07.032 – volume: 588 start-page: 1423 year: 2014 ident: ref_26 article-title: Specific Cx43 phosphorylation events regulate gap junction turnover in vivo publication-title: FEBS Lett. doi: 10.1016/j.febslet.2014.01.049 – ident: ref_1 doi: 10.3390/ijms20061475 – volume: 44 start-page: 716 year: 2019 ident: ref_55 article-title: Pannexin 1 Channels Contribute to IL-1β Expression via NLRP3/Caspase-1 Inflammasome in Aspergillus Fumigatus Keratitis publication-title: Curr. Eye Res. doi: 10.1080/02713683.2019.1584321 – volume: 35 start-page: 284 year: 2019 ident: ref_22 article-title: Silencing KRT16 inhibits keratinocyte proliferation and VEGF secretion in psoriasis via inhibition of ERK signaling pathway publication-title: Kaohsiung J. Med. Sci. doi: 10.1002/kjm2.12034 – volume: 8 start-page: e011006 year: 2019 ident: ref_59 article-title: Systemic Inflammation Rapidly Induces Reversible Atrial Electrical Remodeling: The Role of Interleukin-6–Mediated Changes in Connexin Expression publication-title: J. Am. Heart Assoc. doi: 10.1161/JAHA.118.011006 – volume: 432 start-page: 133 year: 2010 ident: ref_15 article-title: Peptidoglycan derived from Staphylococcus epidermidis induces Connexin43 hemichannel activity with consequences on the innate immune response in endothelial cells publication-title: Biochem. J. doi: 10.1042/BJ20091753 – volume: 132 start-page: 745 year: 1995 ident: ref_61 article-title: Soluble E-cadherin: A novel cutaneous disease marker publication-title: Br. J. Dermatol. doi: 10.1111/j.1365-2133.1995.tb00720.x – volume: 132 start-page: 526 year: 2012 ident: ref_27 article-title: Purinergic Signaling in Healthy and Diseased Skin publication-title: J. Investig. Dermatol. doi: 10.1038/jid.2011.344 – volume: 119 start-page: 5193 year: 2006 ident: ref_31 article-title: Acute downregulation of connexin43 at wound sites leads to a reduced inflammatory response, enhanced keratinocyte proliferation and wound fibroblast migration publication-title: J. Cell Sci. doi: 10.1242/jcs.03320 – volume: 147 start-page: S172 year: 2006 ident: ref_51 article-title: Purinergic signalling publication-title: Br. J. Pharmacol. doi: 10.1038/sj.bjp.0706429 – volume: 25 start-page: 616 year: 2007 ident: ref_4 article-title: Innate immunity and antimicrobial defense systems in psoriasis publication-title: Clin. Dermatol. doi: 10.1016/j.clindermatol.2007.08.016 – volume: 498 start-page: 367 year: 2013 ident: ref_33 article-title: Topographic diversity of fungal and bacterial communities in human skin publication-title: Nature doi: 10.1038/nature12171 – ident: ref_25 doi: 10.1186/1471-2105-13-S2-S11 – volume: 50 start-page: 40 year: 2016 ident: ref_60 article-title: Kinase programs spatiotemporally regulate gap junction assembly and disassembly: Effects on wound repair publication-title: Semin. Cell Dev. Biol. doi: 10.1016/j.semcdb.2015.12.010 – volume: 98 start-page: 428 year: 2018 ident: ref_2 article-title: Significant Changes in the Skin Microbiome in Patients with Chronic Plaque Psoriasis after Treatment with Narrowband Ultraviolet B publication-title: Acta Derm. Venereol. doi: 10.2340/00015555-2859 – volume: 10 start-page: 1 year: 2019 ident: ref_6 article-title: Microbe-host interplay in atopic dermatitis and psoriasis publication-title: Nat. Commun. doi: 10.1038/s41467-019-12253-y – volume: 51 start-page: 413 year: 2016 ident: ref_13 article-title: Con-nexins and their channels in inflammation publication-title: Crit. Rev. Biochem. Mol. Biol. doi: 10.1080/10409238.2016.1204980 – volume: 119 start-page: 1034 year: 2002 ident: ref_50 article-title: P2X purinergic receptor antagonist accelerates skin barrier repair and prevents epidermal hyperplasia induced by skin barrier disruption publication-title: J. Investig. Dermatol. doi: 10.1046/j.1523-1747.2002.19505.x – volume: 21 start-page: 592 year: 2012 ident: ref_16 article-title: Differential susceptibility of Cx26 mutations associated with epidermal dysplasias to peptidoglycan derived from Staphylococcus aureus and Staphylococcus epidermidis publication-title: Exp. Dermatol. doi: 10.1111/j.1600-0625.2012.01521.x – volume: 5 start-page: 7 year: 2015 ident: ref_24 article-title: Diagnostic utility of Ki-67 and Cyclin D1 immunostaining in differentiation of psoriasis vs. other psoriasiform dermatitis publication-title: Dermatol. Pract. Concept. doi: 10.5826/dpc.0503a02 – volume: 227 start-page: 77 year: 2012 ident: ref_65 article-title: The connexin mimetic peptide Gap27 increases human dermal fibroblast migration in hyperglycemic and hyperinsulinemic conditions in vitro publication-title: J. Cell Physiol. doi: 10.1002/jcp.22705 |
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