IL-1beta signals through the EGF receptor and activates Egr-1 through MMP-ADAM

The immediate-early gene Egr-1 controls the inducible expression of many genes implicated in the pathogenesis of a range of vascular disorders, yet our understanding of the mechanisms controlling the rapid expression of this prototypic zinc finger transcription factor is poor. Here we show that Egr-...

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Published in:PloS one 2012-07, Vol.7 (7), p.e39811-e39811
Main Authors: Sanchez-Guerrero, Estella, Chen, Elya, Kockx, Maaike, An, Si-Wei, Chong, Beng H, Khachigian, Levon M
Format: Article
Language:English
Subjects:
ADAM protein
ADAM Proteins - antagonists & inhibitors
ADAM Proteins - metabolism
Animals
Atherosclerosis
Biology
Cytokines
Dipeptides - pharmacology
DNA binding proteins
Early Growth Response Protein 1 - genetics
Early Growth Response Protein 1 - metabolism
EGR-1 protein
Embryo fibroblasts
Embryos
Epidermal growth factor
Epidermal growth factor receptors
Epidermal growth factors
Fibroblasts
Gene expression
Genes
Helicobacter pylori
Humans
Interleukin 1
Interleukin 1 receptors
Interleukin-1beta - metabolism
Interleukin-1beta - pharmacology
Ischemia
Kinases
Ligands
Matrix Metalloproteinases - metabolism
Medicine
Myocytes, Smooth Muscle - drug effects
Myocytes, Smooth Muscle - metabolism
Pathogenesis
Pharmacology
Phosphorylation
Polyclonal antibodies
Protein-tyrosine kinase
Quinazolines - pharmacology
Rats
Receptor, Epidermal Growth Factor - antagonists & inhibitors
Receptor, Epidermal Growth Factor - metabolism
Rodents
Signal transduction
Signal Transduction - drug effects
siRNA
Tyrosine
Tyrphostins - pharmacology
Veins & arteries
Wound healing
Zinc
Zinc finger proteins
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cited_by cdi_FETCH-LOGICAL-c692t-845a0345740a33a8f4ed41e2bd5d1bae1882ba2e759d9b71610a5fc9ba3f6a1e3
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container_end_page e39811
container_issue 7
container_start_page e39811
container_title PloS one
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creator Sanchez-Guerrero, Estella
Chen, Elya
Kockx, Maaike
An, Si-Wei
Chong, Beng H
Khachigian, Levon M
description The immediate-early gene Egr-1 controls the inducible expression of many genes implicated in the pathogenesis of a range of vascular disorders, yet our understanding of the mechanisms controlling the rapid expression of this prototypic zinc finger transcription factor is poor. Here we show that Egr-1 expression induced by IL-1beta is dependent on metalloproteinases (MMP) and a disintegrin and a metalloproteinase (ADAM). Pharmacologic MMP/ADAM inhibitors and siRNA knockdown prevent IL-1beta induction of Egr-1. Further, IL-1beta activates Egr-1 via the epidermal growth factor receptor (EGFR). This is blocked by EGFR tyrosine kinase inhibition and EGFR knockdown. IL-1beta induction of Egr-1 expression is reduced in murine embryonic fibroblasts (mEFs) deficient in ADAM17 despite unbiased expression of EGFR and IL-1RI in ADAM17-deficient and wild-type mEFs. Finally, we show that IL-1beta-inducible wound repair after mechanical injury requires both EGFR and MMP/ADAM. This study reports for the first time that Egr-1 induction by IL-1beta involves EGFR and MMP/ADAM-dependent EGFR phosphorylation.
doi_str_mv 10.1371/journal.pone.0039811
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IL-1beta induction of Egr-1 expression is reduced in murine embryonic fibroblasts (mEFs) deficient in ADAM17 despite unbiased expression of EGFR and IL-1RI in ADAM17-deficient and wild-type mEFs. Finally, we show that IL-1beta-inducible wound repair after mechanical injury requires both EGFR and MMP/ADAM. 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Further, IL-1beta activates Egr-1 via the epidermal growth factor receptor (EGFR). This is blocked by EGFR tyrosine kinase inhibition and EGFR knockdown. IL-1beta induction of Egr-1 expression is reduced in murine embryonic fibroblasts (mEFs) deficient in ADAM17 despite unbiased expression of EGFR and IL-1RI in ADAM17-deficient and wild-type mEFs. Finally, we show that IL-1beta-inducible wound repair after mechanical injury requires both EGFR and MMP/ADAM. This study reports for the first time that Egr-1 induction by IL-1beta involves EGFR and MMP/ADAM-dependent EGFR phosphorylation.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>22792188</pmid><doi>10.1371/journal.pone.0039811</doi><tpages>e39811</tpages><oa>free_for_read</oa></addata></record>
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1932-6203
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subjects ADAM protein
ADAM Proteins - antagonists & inhibitors
ADAM Proteins - metabolism
Animals
Atherosclerosis
Biology
Cytokines
Dipeptides - pharmacology
DNA binding proteins
Early Growth Response Protein 1 - genetics
Early Growth Response Protein 1 - metabolism
EGR-1 protein
Embryo fibroblasts
Embryos
Epidermal growth factor
Epidermal growth factor receptors
Epidermal growth factors
Fibroblasts
Gene expression
Genes
Helicobacter pylori
Humans
Interleukin 1
Interleukin 1 receptors
Interleukin-1beta - metabolism
Interleukin-1beta - pharmacology
Ischemia
Kinases
Ligands
Matrix Metalloproteinases - metabolism
Medicine
Myocytes, Smooth Muscle - drug effects
Myocytes, Smooth Muscle - metabolism
Pathogenesis
Pharmacology
Phosphorylation
Polyclonal antibodies
Protein-tyrosine kinase
Quinazolines - pharmacology
Rats
Receptor, Epidermal Growth Factor - antagonists & inhibitors
Receptor, Epidermal Growth Factor - metabolism
Rodents
Signal transduction
Signal Transduction - drug effects
siRNA
Tyrosine
Tyrphostins - pharmacology
Veins & arteries
Wound healing
Zinc
Zinc finger proteins
title IL-1beta signals through the EGF receptor and activates Egr-1 through MMP-ADAM
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