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ALTERATION OF THE EPHA2/EPHRIN-A SIGNALING AXIS IN PSORIATIC EPIDERMIS

EphA2 is a receptor tyrosine kinase (RTK) that triggers keratinocyte differentiation upon activation and subsequently down-regulation by ephrin-A1 ligand. The objective for this study was to determine if the EphA2/ephrin-A1 signaling axis was altered in psoriasis, an inflammatory skin condition wher...

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Autores principales: Gordon, Kristin, Kochkodan, James J., Blatt, Hanz, Lin, Samantha Y., Kaplan, Nihal, Johnston, Andrew, Swindell, William R., Hoover, Paul, Schlosser, Bethanee J., Elder, James T., Gudjonsson, Johann E., Getsios, Spiro
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3570705/
https://www.ncbi.nlm.nih.gov/pubmed/23190894
http://dx.doi.org/10.1038/jid.2012.391
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author Gordon, Kristin
Kochkodan, James J.
Blatt, Hanz
Lin, Samantha Y.
Kaplan, Nihal
Johnston, Andrew
Swindell, William R.
Hoover, Paul
Schlosser, Bethanee J.
Elder, James T.
Gudjonsson, Johann E.
Getsios, Spiro
author_facet Gordon, Kristin
Kochkodan, James J.
Blatt, Hanz
Lin, Samantha Y.
Kaplan, Nihal
Johnston, Andrew
Swindell, William R.
Hoover, Paul
Schlosser, Bethanee J.
Elder, James T.
Gudjonsson, Johann E.
Getsios, Spiro
author_sort Gordon, Kristin
collection PubMed
description EphA2 is a receptor tyrosine kinase (RTK) that triggers keratinocyte differentiation upon activation and subsequently down-regulation by ephrin-A1 ligand. The objective for this study was to determine if the EphA2/ephrin-A1 signaling axis was altered in psoriasis, an inflammatory skin condition where keratinocyte differentiation is abnormal. Microarray analysis of skin biopsies from psoriasis patients revealed increased mRNA transcripts for several members of this RTK family in plaques, including the EphA1, EphA2 and EphA4 subtypes prominently expressed by keratinocytes. Of these, EphA2 showed the greatest up-regulation, a finding that was confirmed by quantitative RT-PCR, IHC analysis and ELISA. In contrast, psoriatic lesions exhibited reduced ephrin-A ligand immunoreactivity. Exposure of primary keratinocytes induced to differentiated in high calcium or a 3-dimensiosnal raft culture of human epidermis to a combination of growth factors and cytokines elevated in psoriasis increased EphA2 mRNA and protein expression while inducing S100A7 and disrupting differentiation. Pharmacological delivery of a soluble ephrin-A1 peptidomimetic ligand led to a reduction in EphA2 expression and ameliorated proliferation and differentiation in raft cultures exposed to EGF and IL-1α. These findings suggest that ephrin-A1-mediated down-regulation of EphA2 supports keratinocyte differentiation in the context of cytokine perturbation.
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spelling pubmed-35707052013-09-01 ALTERATION OF THE EPHA2/EPHRIN-A SIGNALING AXIS IN PSORIATIC EPIDERMIS Gordon, Kristin Kochkodan, James J. Blatt, Hanz Lin, Samantha Y. Kaplan, Nihal Johnston, Andrew Swindell, William R. Hoover, Paul Schlosser, Bethanee J. Elder, James T. Gudjonsson, Johann E. Getsios, Spiro J Invest Dermatol Article EphA2 is a receptor tyrosine kinase (RTK) that triggers keratinocyte differentiation upon activation and subsequently down-regulation by ephrin-A1 ligand. The objective for this study was to determine if the EphA2/ephrin-A1 signaling axis was altered in psoriasis, an inflammatory skin condition where keratinocyte differentiation is abnormal. Microarray analysis of skin biopsies from psoriasis patients revealed increased mRNA transcripts for several members of this RTK family in plaques, including the EphA1, EphA2 and EphA4 subtypes prominently expressed by keratinocytes. Of these, EphA2 showed the greatest up-regulation, a finding that was confirmed by quantitative RT-PCR, IHC analysis and ELISA. In contrast, psoriatic lesions exhibited reduced ephrin-A ligand immunoreactivity. Exposure of primary keratinocytes induced to differentiated in high calcium or a 3-dimensiosnal raft culture of human epidermis to a combination of growth factors and cytokines elevated in psoriasis increased EphA2 mRNA and protein expression while inducing S100A7 and disrupting differentiation. Pharmacological delivery of a soluble ephrin-A1 peptidomimetic ligand led to a reduction in EphA2 expression and ameliorated proliferation and differentiation in raft cultures exposed to EGF and IL-1α. These findings suggest that ephrin-A1-mediated down-regulation of EphA2 supports keratinocyte differentiation in the context of cytokine perturbation. 2012-11-29 2013-03 /pmc/articles/PMC3570705/ /pubmed/23190894 http://dx.doi.org/10.1038/jid.2012.391 Text en http://www.nature.com/authors/editorial_policies/license.html#terms Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
Gordon, Kristin
Kochkodan, James J.
Blatt, Hanz
Lin, Samantha Y.
Kaplan, Nihal
Johnston, Andrew
Swindell, William R.
Hoover, Paul
Schlosser, Bethanee J.
Elder, James T.
Gudjonsson, Johann E.
Getsios, Spiro
ALTERATION OF THE EPHA2/EPHRIN-A SIGNALING AXIS IN PSORIATIC EPIDERMIS
title ALTERATION OF THE EPHA2/EPHRIN-A SIGNALING AXIS IN PSORIATIC EPIDERMIS
title_full ALTERATION OF THE EPHA2/EPHRIN-A SIGNALING AXIS IN PSORIATIC EPIDERMIS
title_fullStr ALTERATION OF THE EPHA2/EPHRIN-A SIGNALING AXIS IN PSORIATIC EPIDERMIS
title_full_unstemmed ALTERATION OF THE EPHA2/EPHRIN-A SIGNALING AXIS IN PSORIATIC EPIDERMIS
title_short ALTERATION OF THE EPHA2/EPHRIN-A SIGNALING AXIS IN PSORIATIC EPIDERMIS
title_sort alteration of the epha2/ephrin-a signaling axis in psoriatic epidermis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3570705/
https://www.ncbi.nlm.nih.gov/pubmed/23190894
http://dx.doi.org/10.1038/jid.2012.391
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