IL-1beta Signals through the EGF Receptor and Activates Egr-1 through MMP-ADAM
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{"title"=>"Il-1beta signals through the egf receptor and activates egr-1 through mmp-adam", "type"=>"journal", "authors"=>[{"first_name"=>"Estella", "last_name"=>"Sanchez-Guerrero", "scopus_author_id"=>"23996275900"}, {"first_name"=>"Elya", "last_name"=>"Chen", "scopus_author_id"=>"56315176500"}, {"first_name"=>"Maaike", "last_name"=>"Kockx", "scopus_author_id"=>"7005476112"}, {"first_name"=>"Si Wei", "last_name"=>"An", "scopus_author_id"=>"55308655500"}, {"first_name"=>"Beng H.", "last_name"=>"Chong", "scopus_author_id"=>"7101803569"}, {"first_name"=>"Levon M.", "last_name"=>"Khachigian", "scopus_author_id"=>"26643419000"}], "year"=>2012, "source"=>"PLoS ONE", "identifiers"=>{"pui"=>"365220970", "issn"=>"19326203", "pmid"=>"22792188", "scopus"=>"2-s2.0-84863654020", "isbn"=>"1932-6203 (Electronic)\\r1932-6203 (Linking)", "doi"=>"10.1371/journal.pone.0039811", "sgr"=>"84863654020"}, "id"=>"ab12f23b-134a-32d4-843a-191979139cb1", "abstract"=>"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.", "link"=>"http://www.mendeley.com/research/il1beta-signals-through-egf-receptor-activates-egr1-through-mmpadam", "reader_count"=>11, "reader_count_by_academic_status"=>{"Researcher"=>2, "Student > Ph. D. Student"=>5, "Other"=>1, "Student > Bachelor"=>1, "Professor"=>2}, "reader_count_by_user_role"=>{"Researcher"=>2, "Student > Ph. D. Student"=>5, "Other"=>1, "Student > Bachelor"=>1, "Professor"=>2}, "reader_count_by_subject_area"=>{"Biochemistry, Genetics and Molecular Biology"=>1, "Agricultural and Biological Sciences"=>5, "Medicine and Dentistry"=>4, "Business, Management and Accounting"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>4}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>5}, "Business, Management and Accounting"=>{"Business, Management and Accounting"=>1}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>1}}, "group_count"=>0}

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/612626"], "description"=>"<p>Growth-quiescent SMCs were incubated with GM6001+ or GM6001- (25 µM), TAPI-1 (10 µM), AG1478 (5 µM), PD153035 (5 µM) or vehicle for 30 min followed by <i>in vitro</i> scraping injury and addition of IL-1beta (10 ng/ml). Photographs of the denuded zone were taken at 24 h.</p>", "links"=>[], "tags"=>["egfr", "inhibitors", "smc"], "article_id"=>283117, "categories"=>["Molecular Biology", "Biochemistry", "Cell Biology", "Biological Sciences"], "users"=>["Estella Sanchez-Guerrero", "Elya Chen", "Maaike Kockx", "Si-Wei An", "Beng H. Chong", "Levon M. Khachigian"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0039811.g005", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_MMP_and_EGFR_inhibitors_block_SMC_wound_repair_/283117", "title"=>"MMP and EGFR inhibitors block SMC wound repair.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-07-06 00:51:57"}
  • {"files"=>["https://ndownloader.figshare.com/files/612284"], "description"=>"<p>Growth-quiescent SMCs were incubated with EGFR inhibitors AG1478 (5 µM) and PD153035 (5 µM) for 30 min, and exposed to IL-1beta (10 ng/ml) for another 30 min (unless indicated otherwise). (<b>A</b>) Egr-1 mRNA levels in AG1478- and PD153035-treated SMCs incubated with IL-1beta by qPCR. Data were normalized to beta-actin. (<b>B</b>) Western blotting for Egr-1 or beta-actin of total extracts of SMCs treated with AG1478 or PD153035. (<b>C</b>) Western blotting for EGFR, Egr-1 or beta-actin of total extracts of SMCs transfected overnight with EGFR siRNA (0.1 µM) and treated with IL-1beta for 30 min. (<b>D</b>) Western blotting for ErbB4, EGFR, Egr-1 or beta-actin of total extracts of SMCs transfected overnight with ErbB4 siRNA (0.1 µM) and treated with IL-1beta for 30 min. (<b>E</b>) Egr-1 mRNA levels in AG825 (10 µM for 30 min)-treated SMCs incubated with IL-1beta for 30 min by qPCR. Data were normalized to beta-actin. (<b>F</b>) Western blotting for Egr-1 or beta-actin in total extracts of SMCs pretreated with AG825 (10 µM for 30 min) then stimulated with IL-1beta for another 30 min.</p>", "links"=>[], "tags"=>["egr-1", "il-1beta"], "article_id"=>282778, "categories"=>["Molecular Biology", "Biochemistry", "Cell Biology", "Biological Sciences"], "users"=>["Estella Sanchez-Guerrero", "Elya Chen", "Maaike Kockx", "Si-Wei An", "Beng H. Chong", "Levon M. Khachigian"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0039811.g002", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Induction_of_Egr_1_by_IL_1beta_is_EGFR_dependent_/282778", "title"=>"Induction of Egr-1 by IL-1beta is EGFR-dependent.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-07-06 00:46:18"}
  • {"files"=>["https://ndownloader.figshare.com/files/612401"], "description"=>"<p>(<b>A</b>) Growth-quiescent SMCs were stimulated with IL-1beta (10 ng/ml) for the indicated times. Total protein extracts were resolved by SDS-PAGE and subjected to Western blot analysis using antibodies for Egr-1, EGFR phospho-Tyr<sup>845</sup>, total EGFR and beta-actin. Alternatively, Western blotting for EGFR phospho-Tyr<sup>845</sup> or EGFR of total extracts of SMCs treated with (<b>B</b>) AG1478 (5 µM), (<b>C</b>) GM6001+ or GM6001- (25 µM) (<b>D</b>) TAPI-1 (10 µM), PD153035 (5 µM) for 30 min followed by IL-1beta stimulation for 5 min.</p>", "links"=>[], "tags"=>["trans-activates", "egfr", "time-dependent", "mmp"], "article_id"=>282894, "categories"=>["Molecular Biology", "Biochemistry", "Cell Biology", "Biological Sciences"], "users"=>["Estella Sanchez-Guerrero", "Elya Chen", "Maaike Kockx", "Si-Wei An", "Beng H. Chong", "Levon M. Khachigian"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0039811.g003", "stats"=>{"downloads"=>0, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_IL_1beta_trans_activates_EGFR_in_a_time_dependent_manner_and_it_is_dependent_on_MMP_activity_/282894", "title"=>"IL-1beta trans-activates EGFR in a time-dependent manner and it is dependent on MMP activity.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-07-06 00:48:14"}
  • {"files"=>["https://ndownloader.figshare.com/files/612174"], "description"=>"<p>Growth-quiescent SMCs were treated with MMP inhibitor GM6001+ (25 µM) and TAPI-1 (10 µM) for 30 min before stimulation with IL-1beta (10 ng/ml) for another 30 min (unless indicated otherwise). (<b>A</b>) Egr-1 mRNA levels in GM6001+ or GM6001- treated SMCs treated with IL-1beta by qPCR. Data were normalized to beta-actin. (<b>B</b>) Western blotting for Egr-1 or beta-actin in total extracts of SMCs treated with GM6001+ or GM6001-. (<b>C</b>) Egr-1 mRNA levels in TAPI-1 treated SMCs treated with IL-1beta by qPCR. Data were normalized to beta-actin. (<b>D</b>) Western blotting for Egr-1 or beta-actin of total extracts of SMCs treated with TAPI-1. DMSO was used as a carrier. (<b>E</b>) Western blotting for ADAM17, ADAM10, Egr-1 or beta-actin of total extracts of SMCs transfected overnight with ADAM17 siRNA (0.1 µM) and treated with IL-1beta for 30 min.</p>", "links"=>[], "tags"=>["egr-1"], "article_id"=>282667, "categories"=>["Molecular Biology", "Biochemistry", "Cell Biology", "Biological Sciences"], "users"=>["Estella Sanchez-Guerrero", "Elya Chen", "Maaike Kockx", "Si-Wei An", "Beng H. Chong", "Levon M. Khachigian"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0039811.g001", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_IL_1beta_inducible_Egr_1_expression_is_MMP_ADAM_dependent_/282667", "title"=>"IL-1beta-inducible Egr-1 expression is MMP/ADAM-dependent.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-07-06 00:44:27"}
  • {"files"=>["https://ndownloader.figshare.com/files/612506"], "description"=>"<p>(<b>A</b>) Western blotting for Egr-1, ADAM17, EGFR, IL-1RI or beta-actin using total extracts of growth-quiescent wild-type or ADAM17-deficient mEFs treated with IL-1beta for 30 or 60 min. (<b>B</b>) Interaction of <sup>125</sup>I-IL-1beta with ADAM17WT and ADAM17-deficient cells. Growth-quiescent ADAM17WT and ADAM17−/− mEFs (1.8×10<sup>4</sup> cells/well) were incubated with increasing amounts of <sup>125</sup>I-IL-1beta in 1% BSA/PBS for 1 h at 4°C. The cells were washed and lysed with 1M NaOH prior to assessment of counts in an automated gamma-counter.</p>", "links"=>[], "tags"=>["egr-1"], "article_id"=>282999, "categories"=>["Molecular Biology", "Biochemistry", "Cell Biology", "Biological Sciences"], "users"=>["Estella Sanchez-Guerrero", "Elya Chen", "Maaike Kockx", "Si-Wei An", "Beng H. Chong", "Levon M. Khachigian"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0039811.g004", "stats"=>{"downloads"=>0, "page_views"=>10, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_ADAM17_is_required_for_IL_1beta_8211_inducible_Egr_1_expression_/282999", "title"=>"ADAM17 is required for IL-1beta–inducible Egr-1 expression.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-07-06 00:49:59"}
  • {"files"=>["https://ndownloader.figshare.com/files/320147", "https://ndownloader.figshare.com/files/320186", "https://ndownloader.figshare.com/files/320230", "https://ndownloader.figshare.com/files/320259"], "description"=>"<div><p>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 <u>a d</u>isintegrin <u>a</u>nd a <u>m</u>etalloproteinase (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.</p> </div>", "links"=>[], "tags"=>["il-1beta", "signals", "egf", "receptor", "activates", "egr-1", "mmp-adam"], "article_id"=>123199, "categories"=>["Molecular Biology", "Biochemistry", "Cell Biology", "Biological Sciences"], "users"=>["Estella Sanchez-Guerrero", "Elya Chen", "Maaike Kockx", "Si-Wei An", "Beng H. Chong", "Levon M. Khachigian"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0039811.s001", "https://dx.doi.org/10.1371/journal.pone.0039811.s002", "https://dx.doi.org/10.1371/journal.pone.0039811.s003", "https://dx.doi.org/10.1371/journal.pone.0039811.s004"], "stats"=>{"downloads"=>0, "page_views"=>8, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/IL_1beta_Signals_through_the_EGF_Receptor_and_Activates_Egr_1_through_MMP_ADAM/123199", "title"=>"IL-1beta Signals through the EGF Receptor and Activates Egr-1 through MMP-ADAM", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2012-07-06 00:53:19"}

PMC Usage Stats | Further Information

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Relative Metric

{"start_date"=>"2012-01-01T00:00:00Z", "end_date"=>"2012-12-31T00:00:00Z", "subject_areas"=>[{"subject_area"=>"/Biology and life sciences/Developmental biology", "average_usage"=>[313, 562, 690, 796, 893, 986, 1079, 1173, 1257, 1349, 1429, 1506, 1586, 1661, 1730, 1803, 1876, 1945, 2017, 2091, 2163, 2225, 2294, 2362, 2430]}, {"subject_area"=>"/Biology and life sciences/Genetics", "average_usage"=>[333, 576, 707, 814, 908, 1004, 1104, 1197, 1280, 1370, 1449, 1531, 1603, 1673, 1742, 1817, 1886, 1954, 2025, 2098, 2171, 2234, 2304, 2365, 2431]}, {"subject_area"=>"/Biology and life sciences/Immunology", "average_usage"=>[312, 555, 680, 785, 880, 965, 1057, 1142, 1230, 1312, 1394, 1471, 1547, 1613, 1681, 1743, 1805, 1871, 1941, 2010, 2071, 2128, 2202, 2266, 2323]}, {"subject_area"=>"/Medicine and health sciences/Endocrinology", "average_usage"=>[315, 561, 698, 824, 914, 1014, 1127, 1230, 1339, 1437, 1505, 1602, 1669, 1731, 1794, 1868, 1945, 2023, 2083, 2140, 2231, 2286, 2342, 2407, 2460]}, {"subject_area"=>"/Medicine and health sciences/Physiology", "average_usage"=>[308, 535, 653, 754, 847, 930, 1020, 1103, 1188, 1268, 1351, 1420, 1487, 1550, 1614, 1679, 1757, 1830, 1898, 1961, 2024, 2086, 2150, 2216, 2266]}]}
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