PubMed:23609438 JSONTXT

{"target":"https://pubannotation.org/docs/sourcedb/PubMed/sourceid/23609438","sourcedb":"PubMed","sourceid":"23609438","source_url":"http://www.ncbi.nlm.nih.gov/pubmed/23609438","text":"The intermediate conductance calcium-activated potassium channel KCa3.1 regulates vascular smooth muscle cell proliferation via controlling calcium-dependent signaling.\nThe intermediate conductance calcium-activated potassium channel KCa3.1 contributes to a variety of cell activation processes in pathologies such as inflammation, carcinogenesis, and vascular remodeling. We examined the electrophysiological and transcriptional mechanisms by which KCa3.1 regulates vascular smooth muscle cell (VSMC) proliferation. Platelet-derived growth factor-BB (PDGF)-induced proliferation of human coronary artery VSMCs was attenuated by lowering intracellular Ca(2+) concentration ([Ca(2+)]i) and was enhanced by elevating [Ca(2+)]i. KCa3.1 blockade or knockdown inhibited proliferation by suppressing the rise in [Ca(2+)]i and attenuating the expression of phosphorylated cAMP-response element-binding protein (CREB), c-Fos, and neuron-derived orphan receptor-1 (NOR-1). This antiproliferative effect was abolished by elevating [Ca(2+)]i. KCa3.1 overexpression induced VSMC proliferation, and potentiated PDGF-induced proliferation, by inducing CREB phosphorylation, c-Fos, and NOR-1. Pharmacological stimulation of KCa3.1 unexpectedly suppressed proliferation by abolishing the expression and activity of KCa3.1 and PDGF β-receptors and inhibiting the rise in [Ca(2+)]i. The stimulation also attenuated the levels of phosphorylated CREB, c-Fos, and cyclin expression. After KCa3.1 blockade, the characteristic round shape of VSMCs expressing high l-caldesmon and low calponin-1 (dedifferentiation state) was maintained, whereas KCa3.1 stimulation induced a spindle-shaped cellular appearance, with low l-caldesmon and high calponin-1. In conclusion, KCa3.1 plays an important role in VSMC proliferation via controlling Ca(2+)-dependent signaling pathways, and its modulation may therefore constitute a new therapeutic target for cell proliferative diseases such as atherosclerosis.","tracks":[{"project":"Allie","denotations":[{"id":"SS1_23609438_2_0","span":{"begin":467,"end":494},"obj":"expanded"},{"id":"SS2_23609438_2_0","span":{"begin":496,"end":500},"obj":"abbr"},{"id":"SS1_23609438_3_0","span":{"begin":517,"end":550},"obj":"expanded"},{"id":"SS2_23609438_3_0","span":{"begin":552,"end":556},"obj":"abbr"},{"id":"SS1_23609438_4_0","span":{"begin":865,"end":902},"obj":"expanded"},{"id":"SS2_23609438_4_0","span":{"begin":904,"end":908},"obj":"abbr"},{"id":"SS1_23609438_4_1","span":{"begin":922,"end":954},"obj":"expanded"},{"id":"SS2_23609438_4_1","span":{"begin":956,"end":961},"obj":"abbr"}],"relations":[{"id":"AE1_23609438_2_0","pred":"abbreviatedTo","subj":"SS1_23609438_2_0","obj":"SS2_23609438_2_0"},{"id":"AE1_23609438_3_0","pred":"abbreviatedTo","subj":"SS1_23609438_3_0","obj":"SS2_23609438_3_0"},{"id":"AE1_23609438_4_0","pred":"abbreviatedTo","subj":"SS1_23609438_4_0","obj":"SS2_23609438_4_0"},{"id":"AE1_23609438_4_1","pred":"abbreviatedTo","subj":"SS1_23609438_4_1","obj":"SS2_23609438_4_1"}],"attributes":[{"subj":"SS1_23609438_2_0","pred":"source","obj":"Allie"},{"subj":"SS2_23609438_2_0","pred":"source","obj":"Allie"},{"subj":"SS1_23609438_3_0","pred":"source","obj":"Allie"},{"subj":"SS2_23609438_3_0","pred":"source","obj":"Allie"},{"subj":"SS1_23609438_4_0","pred":"source","obj":"Allie"},{"subj":"SS2_23609438_4_0","pred":"source","obj":"Allie"},{"subj":"SS1_23609438_4_1","pred":"source","obj":"Allie"},{"subj":"SS2_23609438_4_1","pred":"source","obj":"Allie"}]},{"project":"CHEMDNER-training-test","denotations":[{"id":"T1","span":{"begin":198,"end":205},"obj":"SYSTEMATIC"},{"id":"T2","span":{"begin":216,"end":225},"obj":"SYSTEMATIC"},{"id":"T3","span":{"begin":652,"end":658},"obj":"FORMULA"},{"id":"T4","span":{"begin":675,"end":681},"obj":"FORMULA"},{"id":"T5","span":{"begin":716,"end":722},"obj":"FORMULA"},{"id":"T6","span":{"begin":807,"end":813},"obj":"FORMULA"},{"id":"T7","span":{"begin":865,"end":869},"obj":"ABBREVIATION"},{"id":"T8","span":{"begin":1022,"end":1028},"obj":"FORMULA"},{"id":"T9","span":{"begin":1257,"end":1258},"obj":"FORMULA"},{"id":"T10","span":{"begin":1813,"end":1819},"obj":"FORMULA"},{"id":"T1","span":{"begin":66,"end":147},"obj":"SYSTEMATIC"},{"id":"T2","span":{"begin":216,"end":225},"obj":"SYSTEMATIC"},{"id":"T3","span":{"begin":1300,"end":1550},"obj":"SYSTEMATIC"}],"attributes":[{"subj":"T1","pred":"source","obj":"CHEMDNER-training-test"},{"subj":"T2","pred":"source","obj":"CHEMDNER-training-test"},{"subj":"T3","pred":"source","obj":"CHEMDNER-training-test"},{"subj":"T4","pred":"source","obj":"CHEMDNER-training-test"},{"subj":"T5","pred":"source","obj":"CHEMDNER-training-test"},{"subj":"T6","pred":"source","obj":"CHEMDNER-training-test"},{"subj":"T7","pred":"source","obj":"CHEMDNER-training-test"},{"subj":"T8","pred":"source","obj":"CHEMDNER-training-test"},{"subj":"T9","pred":"source","obj":"CHEMDNER-training-test"},{"subj":"T10","pred":"source","obj":"CHEMDNER-training-test"},{"subj":"T1","pred":"source","obj":"CHEMDNER-training-test"},{"subj":"T2","pred":"source","obj":"CHEMDNER-training-test"},{"subj":"T3","pred":"source","obj":"CHEMDNER-training-test"}]},{"project":"PubmedHPO","denotations":[{"id":"T1","span":{"begin":1959,"end":1974},"obj":"HP_0002621"}],"attributes":[{"subj":"T1","pred":"source","obj":"PubmedHPO"}]},{"project":"DisGeNET","denotations":[{"id":"T0","span":{"begin":1744,"end":1750},"obj":"gene:3783"},{"id":"T1","span":{"begin":1959,"end":1974},"obj":"disease:C0003850"},{"id":"T2","span":{"begin":1744,"end":1750},"obj":"gene:3783"},{"id":"T3","span":{"begin":1959,"end":1974},"obj":"disease:C0004153"}],"relations":[{"id":"R1","pred":"associated_with","subj":"T0","obj":"T1"},{"id":"R2","pred":"associated_with","subj":"T2","obj":"T3"}],"namespaces":[{"prefix":"gene","uri":"http://www.ncbi.nlm.nih.gov/gene/"},{"prefix":"disease","uri":"http://purl.bioontology.org/ontology/MEDLINEPLUS/"}],"attributes":[{"subj":"T0","pred":"source","obj":"DisGeNET"},{"subj":"T1","pred":"source","obj":"DisGeNET"},{"subj":"T2","pred":"source","obj":"DisGeNET"},{"subj":"T3","pred":"source","obj":"DisGeNET"}]},{"project":"sentences","denotations":[{"id":"T1","span":{"begin":0,"end":168},"obj":"Sentence"},{"id":"T2","span":{"begin":169,"end":372},"obj":"Sentence"},{"id":"T3","span":{"begin":373,"end":516},"obj":"Sentence"},{"id":"T4","span":{"begin":517,"end":725},"obj":"Sentence"},{"id":"T5","span":{"begin":726,"end":963},"obj":"Sentence"},{"id":"T6","span":{"begin":964,"end":1031},"obj":"Sentence"},{"id":"T7","span":{"begin":1032,"end":1177},"obj":"Sentence"},{"id":"T8","span":{"begin":1178,"end":1364},"obj":"Sentence"},{"id":"T9","span":{"begin":1365,"end":1461},"obj":"Sentence"},{"id":"T10","span":{"begin":1462,"end":1728},"obj":"Sentence"},{"id":"T11","span":{"begin":1729,"end":1975},"obj":"Sentence"}],"namespaces":[{"prefix":"_base","uri":"http://pubannotation.org/ontology/tao.owl#"}],"attributes":[{"subj":"T1","pred":"source","obj":"sentences"},{"subj":"T2","pred":"source","obj":"sentences"},{"subj":"T3","pred":"source","obj":"sentences"},{"subj":"T4","pred":"source","obj":"sentences"},{"subj":"T5","pred":"source","obj":"sentences"},{"subj":"T6","pred":"source","obj":"sentences"},{"subj":"T7","pred":"source","obj":"sentences"},{"subj":"T8","pred":"source","obj":"sentences"},{"subj":"T9","pred":"source","obj":"sentences"},{"subj":"T10","pred":"source","obj":"sentences"},{"subj":"T11","pred":"source","obj":"sentences"}]},{"project":"NCBITAXON","denotations":[{"id":"T1","span":{"begin":583,"end":588},"obj":"OrganismTaxon"}],"attributes":[{"id":"A1","pred":"db_id","subj":"T1","obj":"9606"},{"subj":"T1","pred":"source","obj":"NCBITAXON"}]},{"project":"DisGeNET5_gene_disease","denotations":[{"id":"23609438-7#81#90#gene800","span":{"begin":1543,"end":1552},"obj":"gene800"},{"id":"23609438-7#99#109#gene1264","span":{"begin":1561,"end":1571},"obj":"gene1264"},{"id":"23609438-7#236#245#gene800","span":{"begin":1698,"end":1707},"obj":"gene800"},{"id":"23609438-7#255#265#gene1264","span":{"begin":1717,"end":1727},"obj":"gene1264"},{"id":"23609438-7#111#128#diseaseC0002793","span":{"begin":1573,"end":1590},"obj":"diseaseC0002793"}],"relations":[{"id":"81#90#gene800111#128#diseaseC0002793","pred":"associated_with","subj":"23609438-7#81#90#gene800","obj":"23609438-7#111#128#diseaseC0002793"},{"id":"99#109#gene1264111#128#diseaseC0002793","pred":"associated_with","subj":"23609438-7#99#109#gene1264","obj":"23609438-7#111#128#diseaseC0002793"},{"id":"236#245#gene800111#128#diseaseC0002793","pred":"associated_with","subj":"23609438-7#236#245#gene800","obj":"23609438-7#111#128#diseaseC0002793"},{"id":"255#265#gene1264111#128#diseaseC0002793","pred":"associated_with","subj":"23609438-7#255#265#gene1264","obj":"23609438-7#111#128#diseaseC0002793"}],"attributes":[{"subj":"23609438-7#81#90#gene800","pred":"source","obj":"DisGeNET5_gene_disease"},{"subj":"23609438-7#99#109#gene1264","pred":"source","obj":"DisGeNET5_gene_disease"},{"subj":"23609438-7#236#245#gene800","pred":"source","obj":"DisGeNET5_gene_disease"},{"subj":"23609438-7#255#265#gene1264","pred":"source","obj":"DisGeNET5_gene_disease"},{"subj":"23609438-7#111#128#diseaseC0002793","pred":"source","obj":"DisGeNET5_gene_disease"}]},{"project":"mondo_disease","denotations":[{"id":"T1","span":{"begin":318,"end":330},"obj":"Disease"},{"id":"T2","span":{"begin":1959,"end":1974},"obj":"Disease"}],"attributes":[{"id":"A1","pred":"mondo_id","subj":"T1","obj":"http://purl.obolibrary.org/obo/MONDO_0021166"},{"id":"A2","pred":"mondo_id","subj":"T2","obj":"http://purl.obolibrary.org/obo/MONDO_0005311"},{"subj":"T1","pred":"source","obj":"mondo_disease"},{"subj":"T2","pred":"source","obj":"mondo_disease"}]},{"project":"Glycosmos6-MAT","denotations":[{"id":"T1","span":{"begin":91,"end":104},"obj":"http://purl.obolibrary.org/obo/MAT_0000303"},{"id":"T2","span":{"begin":98,"end":104},"obj":"http://purl.obolibrary.org/obo/MAT_0000025"},{"id":"T3","span":{"begin":476,"end":489},"obj":"http://purl.obolibrary.org/obo/MAT_0000303"},{"id":"T4","span":{"begin":483,"end":489},"obj":"http://purl.obolibrary.org/obo/MAT_0000025"},{"id":"T5","span":{"begin":598,"end":604},"obj":"http://purl.obolibrary.org/obo/MAT_0000034"}],"attributes":[{"subj":"T1","pred":"source","obj":"Glycosmos6-MAT"},{"subj":"T2","pred":"source","obj":"Glycosmos6-MAT"},{"subj":"T3","pred":"source","obj":"Glycosmos6-MAT"},{"subj":"T4","pred":"source","obj":"Glycosmos6-MAT"},{"subj":"T5","pred":"source","obj":"Glycosmos6-MAT"}]},{"project":"Inflammaging","denotations":[{"id":"T1","span":{"begin":0,"end":168},"obj":"Sentence"},{"id":"T2","span":{"begin":169,"end":372},"obj":"Sentence"},{"id":"T3","span":{"begin":373,"end":516},"obj":"Sentence"},{"id":"T4","span":{"begin":517,"end":725},"obj":"Sentence"},{"id":"T5","span":{"begin":726,"end":963},"obj":"Sentence"},{"id":"T6","span":{"begin":964,"end":1031},"obj":"Sentence"},{"id":"T7","span":{"begin":1032,"end":1177},"obj":"Sentence"},{"id":"T8","span":{"begin":1178,"end":1364},"obj":"Sentence"},{"id":"T9","span":{"begin":1365,"end":1461},"obj":"Sentence"},{"id":"T10","span":{"begin":1462,"end":1728},"obj":"Sentence"},{"id":"T11","span":{"begin":1729,"end":1975},"obj":"Sentence"},{"id":"T1","span":{"begin":0,"end":168},"obj":"Sentence"},{"id":"T2","span":{"begin":169,"end":372},"obj":"Sentence"},{"id":"T3","span":{"begin":373,"end":516},"obj":"Sentence"},{"id":"T4","span":{"begin":517,"end":725},"obj":"Sentence"},{"id":"T5","span":{"begin":726,"end":963},"obj":"Sentence"},{"id":"T6","span":{"begin":964,"end":1031},"obj":"Sentence"},{"id":"T7","span":{"begin":1032,"end":1177},"obj":"Sentence"},{"id":"T8","span":{"begin":1178,"end":1364},"obj":"Sentence"},{"id":"T9","span":{"begin":1365,"end":1461},"obj":"Sentence"},{"id":"T10","span":{"begin":1462,"end":1728},"obj":"Sentence"},{"id":"T11","span":{"begin":1729,"end":1975},"obj":"Sentence"}],"attributes":[{"subj":"T1","pred":"source","obj":"Inflammaging"},{"subj":"T2","pred":"source","obj":"Inflammaging"},{"subj":"T3","pred":"source","obj":"Inflammaging"},{"subj":"T4","pred":"source","obj":"Inflammaging"},{"subj":"T5","pred":"source","obj":"Inflammaging"},{"subj":"T6","pred":"source","obj":"Inflammaging"},{"subj":"T7","pred":"source","obj":"Inflammaging"},{"subj":"T8","pred":"source","obj":"Inflammaging"},{"subj":"T9","pred":"source","obj":"Inflammaging"},{"subj":"T10","pred":"source","obj":"Inflammaging"},{"subj":"T11","pred":"source","obj":"Inflammaging"},{"subj":"T1","pred":"source","obj":"Inflammaging"},{"subj":"T2","pred":"source","obj":"Inflammaging"},{"subj":"T3","pred":"source","obj":"Inflammaging"},{"subj":"T4","pred":"source","obj":"Inflammaging"},{"subj":"T5","pred":"source","obj":"Inflammaging"},{"subj":"T6","pred":"source","obj":"Inflammaging"},{"subj":"T7","pred":"source","obj":"Inflammaging"},{"subj":"T8","pred":"source","obj":"Inflammaging"},{"subj":"T9","pred":"source","obj":"Inflammaging"},{"subj":"T10","pred":"source","obj":"Inflammaging"},{"subj":"T11","pred":"source","obj":"Inflammaging"}]},{"project":"Anatomy-MAT","denotations":[{"id":"T1","span":{"begin":91,"end":104},"obj":"Body_part"},{"id":"T2","span":{"begin":476,"end":489},"obj":"Body_part"},{"id":"T3","span":{"begin":598,"end":604},"obj":"Body_part"}],"attributes":[{"id":"A1","pred":"mat_id","subj":"T1","obj":"http://purl.obolibrary.org/obo/MAT_0000303"},{"id":"A2","pred":"mat_id","subj":"T2","obj":"http://purl.obolibrary.org/obo/MAT_0000303"},{"id":"A3","pred":"mat_id","subj":"T3","obj":"http://purl.obolibrary.org/obo/MAT_0000034"},{"subj":"T1","pred":"source","obj":"Anatomy-MAT"},{"subj":"T2","pred":"source","obj":"Anatomy-MAT"},{"subj":"T3","pred":"source","obj":"Anatomy-MAT"}]},{"project":"Anatomy-UBERON","denotations":[{"id":"T1","span":{"begin":82,"end":109},"obj":"Body_part"},{"id":"T2","span":{"begin":467,"end":494},"obj":"Body_part"},{"id":"T3","span":{"begin":496,"end":500},"obj":"Body_part"},{"id":"T4","span":{"begin":517,"end":525},"obj":"Body_part"},{"id":"T5","span":{"begin":589,"end":604},"obj":"Body_part"},{"id":"T6","span":{"begin":638,"end":651},"obj":"Body_part"},{"id":"T7","span":{"begin":922,"end":928},"obj":"Body_part"},{"id":"T8","span":{"begin":1062,"end":1066},"obj":"Body_part"},{"id":"T9","span":{"begin":1778,"end":1782},"obj":"Body_part"}],"attributes":[{"id":"A1","pred":"uberon_id","subj":"T1","obj":"http://purl.obolibrary.org/obo/CL_0000359"},{"id":"A2","pred":"uberon_id","subj":"T2","obj":"http://purl.obolibrary.org/obo/CL_0000359"},{"id":"A3","pred":"uberon_id","subj":"T3","obj":"http://purl.obolibrary.org/obo/CL_0000359"},{"id":"A4","pred":"uberon_id","subj":"T4","obj":"http://purl.obolibrary.org/obo/CL_0000233"},{"id":"A5","pred":"uberon_id","subj":"T5","obj":"http://purl.obolibrary.org/obo/UBERON_0001621"},{"id":"A6","pred":"uberon_id","subj":"T6","obj":"http://purl.obolibrary.org/obo/GO_0005622"},{"id":"A7","pred":"uberon_id","subj":"T7","obj":"http://purl.obolibrary.org/obo/CL_0000540"},{"id":"A8","pred":"uberon_id","subj":"T8","obj":"http://purl.obolibrary.org/obo/CL_0000359"},{"id":"A9","pred":"uberon_id","subj":"T9","obj":"http://purl.obolibrary.org/obo/CL_0000359"},{"subj":"T1","pred":"source","obj":"Anatomy-UBERON"},{"subj":"T2","pred":"source","obj":"Anatomy-UBERON"},{"subj":"T3","pred":"source","obj":"Anatomy-UBERON"},{"subj":"T4","pred":"source","obj":"Anatomy-UBERON"},{"subj":"T5","pred":"source","obj":"Anatomy-UBERON"},{"subj":"T6","pred":"source","obj":"Anatomy-UBERON"},{"subj":"T7","pred":"source","obj":"Anatomy-UBERON"},{"subj":"T8","pred":"source","obj":"Anatomy-UBERON"},{"subj":"T9","pred":"source","obj":"Anatomy-UBERON"}]},{"project":"HP-phenotype","denotations":[{"id":"T1","span":{"begin":1959,"end":1974},"obj":"Phenotype"}],"attributes":[{"id":"A1","pred":"hp_id","subj":"T1","obj":"HP:0002621"},{"subj":"T1","pred":"source","obj":"HP-phenotype"}],"namespaces":[{"prefix":"HP","uri":"http://purl.obolibrary.org/obo/HP_"}]},{"project":"CL-cell","denotations":[{"id":"T1","span":{"begin":82,"end":109},"obj":"Cell"},{"id":"T2","span":{"begin":91,"end":109},"obj":"Cell"},{"id":"T3","span":{"begin":98,"end":109},"obj":"Cell"},{"id":"T4","span":{"begin":467,"end":494},"obj":"Cell"},{"id":"T5","span":{"begin":476,"end":494},"obj":"Cell"},{"id":"T6","span":{"begin":483,"end":494},"obj":"Cell"},{"id":"T7","span":{"begin":496,"end":500},"obj":"Cell"},{"id":"T8","span":{"begin":517,"end":525},"obj":"Cell"},{"id":"T9","span":{"begin":922,"end":928},"obj":"Cell"},{"id":"T10","span":{"begin":1062,"end":1066},"obj":"Cell"},{"id":"T11","span":{"begin":1778,"end":1782},"obj":"Cell"}],"attributes":[{"id":"A1","pred":"cl_id","subj":"T1","obj":"http://purl.obolibrary.org/obo/CL:0000359"},{"id":"A2","pred":"cl_id","subj":"T2","obj":"http://purl.obolibrary.org/obo/CL:0000192"},{"id":"A3","pred":"cl_id","subj":"T3","obj":"http://purl.obolibrary.org/obo/CL:0000187"},{"id":"A4","pred":"cl_id","subj":"T4","obj":"http://purl.obolibrary.org/obo/CL:0000359"},{"id":"A5","pred":"cl_id","subj":"T5","obj":"http://purl.obolibrary.org/obo/CL:0000192"},{"id":"A6","pred":"cl_id","subj":"T6","obj":"http://purl.obolibrary.org/obo/CL:0000187"},{"id":"A7","pred":"cl_id","subj":"T7","obj":"http://purl.obolibrary.org/obo/CL:0000359"},{"id":"A8","pred":"cl_id","subj":"T8","obj":"http://purl.obolibrary.org/obo/CL:0000233"},{"id":"A9","pred":"cl_id","subj":"T9","obj":"http://purl.obolibrary.org/obo/CL:0000540"},{"id":"A10","pred":"cl_id","subj":"T10","obj":"http://purl.obolibrary.org/obo/CL:0000359"},{"id":"A11","pred":"cl_id","subj":"T11","obj":"http://purl.obolibrary.org/obo/CL:0000359"},{"subj":"T1","pred":"source","obj":"CL-cell"},{"subj":"T2","pred":"source","obj":"CL-cell"},{"subj":"T3","pred":"source","obj":"CL-cell"},{"subj":"T4","pred":"source","obj":"CL-cell"},{"subj":"T5","pred":"source","obj":"CL-cell"},{"subj":"T6","pred":"source","obj":"CL-cell"},{"subj":"T7","pred":"source","obj":"CL-cell"},{"subj":"T8","pred":"source","obj":"CL-cell"},{"subj":"T9","pred":"source","obj":"CL-cell"},{"subj":"T10","pred":"source","obj":"CL-cell"},{"subj":"T11","pred":"source","obj":"CL-cell"}]}],"config":{"attribute types":[{"pred":"source","value type":"selection","values":[{"id":"Allie","color":"#ec9493","default":true},{"id":"CHEMDNER-training-test","color":"#93abec"},{"id":"PubmedHPO","color":"#c5ec93"},{"id":"DisGeNET","color":"#ec93df"},{"id":"sentences","color":"#93ecdf"},{"id":"NCBITAXON","color":"#ecc593"},{"id":"DisGeNET5_gene_disease","color":"#ab93ec"},{"id":"mondo_disease","color":"#95ec93"},{"id":"Glycosmos6-MAT","color":"#ec93af"},{"id":"Inflammaging","color":"#93c9ec"},{"id":"Anatomy-MAT","color":"#e3ec93"},{"id":"Anatomy-UBERON","color":"#db93ec"},{"id":"HP-phenotype","color":"#93ecc1"},{"id":"CL-cell","color":"#eca793"}]}]}}