Connexin 26 regulates epidermal barrier and wound remodeling and promotes psoriasiform response.

The Journal of Clinical Investigation
Ali R DjalilianJulia A Segre

Abstract

Inflammatory skin disorders result in significant epidermal changes, including keratinocyte hyperproliferation, incomplete differentiation, and impaired barrier. Here we test whether, conversely, an impaired epidermal barrier can promote an inflammatory response. Mice lacking the transcription factor Kruppel-like factor 4 (Klf4) have a severe defect in epidermal barrier acquisition. Transcription profiling of Klf4(-/-) newborn skin revealed similar changes in gene expression to involved psoriatic plaques, including a significant upregulation of the gap junction protein connexin 26 (Cx26). Ectopic expression of Cx26 from the epidermis-specific involucrin (INV) promoter (INV-Cx26) demonstrated that downregulation of Cx26 is required for barrier acquisition during development. In juvenile and adult mice, persistent Cx26 expression kept wounded epidermis in a hyperproliferative state, blocked the transition to remodeling, and led to an infiltration of immune cells. Mechanistically, ectopic expression of Cx26 in keratinocytes resulted in increased ATP release, which delayed epidermal barrier recovery and promoted an inflammatory response in resident immune cells. These results provide a molecular link between barrier acquisition in ...Continue Reading

References

Aug 1, 1992·The Journal of Clinical Investigation·L C WoodK R Feingold
May 1, 1991·The Journal of Clinical Investigation·E ProkschP M Elias
Jun 1, 1993·The Journal of Clinical Investigation·M AszterbaumM L Williams
Dec 31, 1997·The Journal of Clinical Investigation·P W CookM R Pittelkow
Feb 12, 1998·Developmental Dynamics : an Official Publication of the American Association of Anatomists·R ChoudhryM B Hodgins
Jul 17, 1998·The Journal of Investigative Dermatology·M P LabartheD Salomon
Oct 18, 2000·Seminars in Neonatology : SN·P Cartlidge
May 12, 2001·The Journal of Investigative Dermatology·F CaponG Novelli
Sep 7, 2001·Nature Genetics·A J WalleyW O Cookson
Feb 14, 2003·Mammalian Genome : Official Journal of the International Mammalian Genome Society·Satyakam PatelJulia A Segre
Jul 4, 2003·Journal of Cell Science·Markus KretzThomas Ott
Jul 5, 2003·Cell Biology International·Petula CoutinhoDavid Becker
Oct 1, 2003·Nature Genetics·Nobunao WakabayashiMasayuki Yamamoto
Oct 3, 2003·Current Biology : CB·Cindy QiuDavid L Becker
Jun 12, 2004·The Journal of Investigative Dermatology·Richard L EckertSivaprakasam Balasubramanian
Jun 17, 2004·The Journal of Clinical Investigation·Brian J Nickoloff, Frank O Nestle
Jun 24, 2004·Human Molecular Genetics·Guilherme Munhoz EssenfelderGilles Waksman
Jul 13, 2004·The Journal of Investigative Dermatology·Maurice A M van SteenselMichel van Geel
Jul 13, 2004·The Journal of Investigative Dermatology·Jean JaubertJulia A Segre
Jul 30, 2004·Molecular Biology of the Cell·Karen MaassKlaus Willecke
Sep 15, 2004·Current Opinion in Cell Biology·Charles StoutDavid L Paul
Sep 28, 2004·Experimental Dermatology·David P Kelsell
Feb 1, 2005·European Journal of Cell Biology·Markus KretzKlaus Willecke
Feb 15, 2005·Clinics in Dermatology·Gabriele Richard
Apr 9, 2005·The Journal of Investigative Dermatology·Kaori InoueKazuhide Inoue
May 6, 2005·The New England Journal of Medicine·Michael P Schön, W-Henning Boehncke
Aug 16, 2005·The Journal of Investigative Dermatology·Peter M Elias
Aug 25, 2005·The Journal of Investigative Dermatology·Jennifer G GeorgiouRonald Sluyter

❮ Previous
Next ❯

Citations

Jun 22, 2007·The Journal of Membrane Biology·Y K Stella ManDavid P Kelsell
Nov 9, 2011·Nature Reviews. Rheumatology·Darren D O'Rielly, Proton Rahman
Jan 17, 2007·Current Opinion in Pediatrics·Brian P Vickery
Sep 11, 2010·Journal of Pediatric Hematology/oncology·Surya RednamAlberto S Pappo
May 11, 2007·Annual Review of Cell and Developmental Biology·Maranke I Koster, Dennis R Roop
May 4, 2006·The Journal of Clinical Investigation·Julia A Segre
Aug 4, 2006·The Journal of Clinical Investigation·Rachael A Clark, Thomas S Kupper
Mar 29, 2014·Advances in Wound Care·Tongyu Cao WikramanayakeMarjana Tomic-Canic
Nov 30, 2006·Proceedings of the National Academy of Sciences of the United States of America·Satyakam PatelJulia A Segre
Mar 3, 2012·EMBO Molecular Medicine·Matthias SchäferSabine Werner
Mar 13, 2014·FEBS Letters·Christina L GrekGautam S Ghatnekar
Mar 13, 2014·FEBS Letters·Patricia E MartinCatherine S Wright
Apr 25, 2012·The Journal of Cell Biology·Jeremy D Rotty, Pierre A Coulombe
Aug 13, 2015·The British Journal of Dermatology·J E S SutcliffeD L Becker
Apr 13, 2007·The Journal of Investigative Dermatology·Johann E GudjonssonJames T Elder
Oct 16, 2007·The Journal of Investigative Dermatology·Gülistan MeşeThomas W White
Oct 15, 2013·Glia·Anna Nualart-MartiCarles Solsona
Oct 18, 2015·Rheumatic Diseases Clinics of North America·Darren D O'Rielly, Proton Rahman
Aug 30, 2008·Journal of Cutaneous Pathology·Zheng-Hua ZhangZhi-Zhong Zheng
Oct 22, 2008·Cell Motility and the Cytoskeleton·Hayden HuangJeffrey Saffitz
Dec 2, 2008·Experimental Dermatology·Ehrhardt ProkschJens-Michael Jensen
Jun 8, 2011·Birth Defects Research. Part A, Clinical and Molecular Teratology·Jorge A Piedrahita
May 1, 2013·Wound Repair and Regeneration : Official Publication of the Wound Healing Society [and] the European Tissue Repair Society·Nicola G DavisDavid L Becker
Aug 8, 2015·Human Molecular Genetics·Chengyuan TangZhuohua Zhang
Jul 28, 2015·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Noah A Levit, Thomas W White
Aug 13, 2011·The Biochemical Journal·Claire A Scott, David P Kelsell
Dec 14, 2011·Biochimica Et Biophysica Acta·David L BeckerAnthony R J Phillips
Jun 21, 2015·Cellular and Molecular Life Sciences : CMLS·Chrysovalantou FanikuPatricia E Martin
Jan 27, 2015·Cell and Tissue Research·Patricia E M Martin, Maurice van Steensel
Aug 10, 2010·Trends in Genetics : TIG·Elisha D O Roberson, Anne M Bowcock
Sep 22, 2011·Biochimica Et Biophysica Acta·Claire A ScottDavid P Kelsell
Nov 12, 2014·Frontiers in Cellular Neuroscience·Helmuth A Sanchez, Vytas K Verselis
Feb 26, 2016·The Journal of Membrane Biology·Bruno CogliatiMathieu Vinken
Feb 27, 2016·International Forum of Allergy & Rhinology·Raymond KimRichard Douglas
Jul 9, 2016·Critical Reviews in Biochemistry and Molecular Biology·Joost WillebrordsMathieu Vinken

❮ Previous
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Datasets Mentioned

BETA
U20344

Methods Mentioned

BETA
immunoprecipitation
PCR
transgenics
biopsy
transgenic
genotyping
transfection
protein assay
biopsies
Fluorescence Microscopy

Software Mentioned

Openlab
IPLab
Scanalytics
Improvision

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