{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T02:28:59Z","timestamp":1784687339729,"version":"3.55.0"},"reference-count":36,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"10","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["ATVB"],"published-print":{"date-parts":[[2011,10]]},"abstract":"<jats:sec>\n            <jats:title>Objective\u2014<\/jats:title>\n            <jats:p>The tonicity-responsive transcription factor, nuclear factor of activated T cells 5 (NFAT5\/tonicity enhancer binding protein [TonEBP]), has been well characterized in numerous cell types; however, NFAT5 function in vascular smooth muscle cells (SMCs) is unknown. Our main objective was to determine the role of NFAT5 regulation in SMCs.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods and Results\u2014<\/jats:title>\n            <jats:p>\n              We showed that NFAT5 is regulated by hypertonicity in SMCs and is upregulated in atherosclerosis and neointimal hyperplasia. RNAi knockdown of NFAT5 inhibited basal expression of several SMC differentiation marker genes, including smooth muscle \u03b1 actin (SM\u03b1A). Bioinformatic analysis of SM\u03b1A revealed 7 putative NFAT5 binding sites in the first intron, and chromatin immunoprecipitation analysis showed NFAT5 enrichment of intronic DNA. Overexpression of NFAT5 increased SM\u03b1A promoter-intron activity, which requires an NFAT5\n              <jats:italic>cis<\/jats:italic>\n              element at +1012, whereas dominant-negative NFAT5 decreased SM\u03b1A promoter-intron activity. Because it is unlikely that SMCs experience extreme changes in tonicity, we investigated other stimuli and uncovered 2 novel NFAT5-inducing factors: angiotensin II, a contractile agonist, and platelet-derived growth factor-BB (PDGF-BB), a potent mitogen in vascular injury. Angiotensin II stimulated NFAT5 translocation and activity, and NFAT5 knockdown inhibited an angiotensin II-mediated upregulation of SM\u03b1A mRNA. PDGF-BB increased NFAT5 protein, and loss of NFAT5 inhibited PDGF-BB-induced SMC migration.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusion\u2014<\/jats:title>\n            <jats:p>We have identified NFAT5 as a novel regulator of SMC phenotypic modulation and have uncovered the role of NFAT5 in angiotensin II-induced SM\u03b1A expression and PDGF-BB-stimulated SMC migration.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/atvbaha.111.232165","type":"journal-article","created":{"date-parts":[[2011,7,15]],"date-time":"2011-07-15T03:07:22Z","timestamp":1310699242000},"page":"2287-2296","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":37,"title":["Nuclear Factor of Activated T Cells 5 Regulates Vascular Smooth Muscle Cell Phenotypic Modulation"],"prefix":"10.1161","volume":"31","author":[{"given":"Julia A.","family":"Halterman","sequence":"first","affiliation":[{"name":"From the Department of Pharmacology (J.A.H., B.R.W.), Robert M. Berne Cardiovascular Research Center (J.A.H., P.D.S.B., B.R.W.), and Department of Medicine, Cardiovascular Division (R.Z., P.D.S.B., B.R.W.), University of Virginia, Charlottesville, VA; Department of Medicine, University of Maryland School of Medicine, Baltimore, MD (H.M.K.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H. Moo","family":"Kwon","sequence":"additional","affiliation":[{"name":"From the Department of Pharmacology (J.A.H., B.R.W.), Robert M. Berne Cardiovascular Research Center (J.A.H., P.D.S.B., B.R.W.), and Department of Medicine, Cardiovascular Division (R.Z., P.D.S.B., B.R.W.), University of Virginia, Charlottesville, VA; Department of Medicine, University of Maryland School of Medicine, Baltimore, MD (H.M.K.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramin","family":"Zargham","sequence":"additional","affiliation":[{"name":"From the Department of Pharmacology (J.A.H., B.R.W.), Robert M. Berne Cardiovascular Research Center (J.A.H., P.D.S.B., B.R.W.), and Department of Medicine, Cardiovascular Division (R.Z., P.D.S.B., B.R.W.), University of Virginia, Charlottesville, VA; Department of Medicine, University of Maryland School of Medicine, Baltimore, MD (H.M.K.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pamela D. Schoppee","family":"Bortz","sequence":"additional","affiliation":[{"name":"From the Department of Pharmacology (J.A.H., B.R.W.), Robert M. Berne Cardiovascular Research Center (J.A.H., P.D.S.B., B.R.W.), and Department of Medicine, Cardiovascular Division (R.Z., P.D.S.B., B.R.W.), University of Virginia, Charlottesville, VA; Department of Medicine, University of Maryland School of Medicine, Baltimore, MD (H.M.K.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian R.","family":"Wamhoff","sequence":"additional","affiliation":[{"name":"From the Department of Pharmacology (J.A.H., B.R.W.), Robert M. Berne Cardiovascular Research Center (J.A.H., P.D.S.B., B.R.W.), and Department of Medicine, Cardiovascular Division (R.Z., P.D.S.B., B.R.W.), University of Virginia, Charlottesville, VA; Department of Medicine, University of Maryland School of Medicine, Baltimore, MD (H.M.K.)."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/16.suppl_I.33"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00041.2003"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.84.7.852"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI26505"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.62.4.749"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.res.0000266448.30370.a0"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.5.2538"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncb816"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.03307"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0403139101"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1186\/ar427"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.13.7214"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.31.19664"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M308795200"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.165.9.4884"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddp511"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M500322200"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M800423200"},{"key":"e_1_3_4_20_2","article-title":"NFAT5 is a critical regulator of inflammatory arthritis","author":"Yoon HJ","unstructured":"Yoon HJ, You S, Yoo SA, Kim NH, Kwon HM, Yoon CH, Cho CS, Hwang D, Kim WU. NFAT5 is a critical regulator of inflammatory arthritis. Arthritis Rheum.","journal-title":"Arthritis Rheum"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.res.0000138582.36921.9e"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0076-6879(07)28014-0"},{"key":"e_1_3_4_23_2","first-page":"208","article-title":"Mechanisms of stenosis after arterial injury","volume":"49","author":"Clowes AW","year":"1983","unstructured":"Clowes AW, Reidy MA, Clowes MM. Mechanisms of stenosis after arterial injury. Lab Invest. 1983;49:208\u2013215.","journal-title":"Lab Invest"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.res.0000068405.49081.09"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.1161\/hh1101.091339"},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.10.2.561"},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.78.3.1695"},{"key":"e_1_3_4_28_2","doi-asserted-by":"publisher","DOI":"10.1023\/A:1006941621170"},{"key":"e_1_3_4_29_2","doi-asserted-by":"publisher","DOI":"10.1002\/j.1460-2075.1987.tb02564.x"},{"key":"e_1_3_4_30_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.res.0000147961.09840.fb"},{"key":"e_1_3_4_31_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00303.2001"},{"key":"e_1_3_4_32_2","doi-asserted-by":"publisher","DOI":"10.1359\/jbmr.070322"},{"key":"e_1_3_4_33_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0801453105"},{"key":"e_1_3_4_34_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M800281200"},{"key":"e_1_3_4_35_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M411972200"},{"key":"e_1_3_4_36_2","doi-asserted-by":"publisher","DOI":"10.1159\/000250095"},{"key":"e_1_3_4_37_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0005245"}],"container-title":["Arteriosclerosis, Thrombosis, and Vascular Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/ATVBAHA.111.232165","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,12]],"date-time":"2024-05-12T23:10:27Z","timestamp":1715555427000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/ATVBAHA.111.232165"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2011,10]]},"references-count":36,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2011,10]]}},"alternative-id":["10.1161\/ATVBAHA.111.232165"],"URL":"https:\/\/doi.org\/10.1161\/atvbaha.111.232165","relation":{},"ISSN":["1079-5642","1524-4636"],"issn-type":[{"value":"1079-5642","type":"print"},{"value":"1524-4636","type":"electronic"}],"subject":[],"published":{"date-parts":[[2011,10]]},"assertion":[{"value":"2011-03-15","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2011-07-01","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2011-07-14","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}