{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T14:22:26Z","timestamp":1781706146877,"version":"3.54.5"},"reference-count":46,"publisher":"American Society for Clinical Investigation","issue":"21","funder":[{"name":"JSPS, AMED-CREAST Japan","award":["Grant Number 15H05788"],"award-info":[{"award-number":["Grant Number 15H05788"]}]},{"DOI":"10.13039\/100009619","name":"AMED","doi-asserted-by":"crossref","award":["JP18ek0210093"],"award-info":[{"award-number":["JP18ek0210093"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2018,11,2]]},"abstract":"<jats:p>\n                    Maternal malnutrition, which causes prenatal exposure to excessive glucocorticoid, induces adverse metabolic programming, leading to hypertension in offspring. In offspring of pregnant rats receiving a low-protein diet or dexamethasone, a synthetic glucocorticoid, mRNA expression of angiotensin receptor type 1a (\n                    <jats:italic>Agtr1a<\/jats:italic>\n                    ) in the paraventricular nucleus (PVN) of the hypothalamus was upregulated, concurrent with reduced expression of DNA methyltransferase 3a (\n                    <jats:italic>Dnmt3a<\/jats:italic>\n                    ), reduced binding of DNMT3a to the\n                    <jats:italic>Agtr1a<\/jats:italic>\n                    gene, and DNA demethylation. Salt loading increased BP in both types of offspring, suggesting that elevated hypothalamic\n                    <jats:italic>Agtr1a<\/jats:italic>\n                    expression is epigenetically modulated by excessive glucocorticoid and leads to adult-onset salt-sensitive hypertension. Consistent with this, dexamethasone treatment of PVN cells upregulated\n                    <jats:italic>Agtr1a<\/jats:italic>\n                    , while downregulating\n                    <jats:italic>Dnmt3a<\/jats:italic>\n                    , and decreased DNMT3a binding and DNA demethylation at the\n                    <jats:italic>Agtr1a<\/jats:italic>\n                    locus. In addition,\n                    <jats:italic>Dnmt3a<\/jats:italic>\n                    knockdown upregulated\n                    <jats:italic>Agtr1a<\/jats:italic>\n                    independently of dexamethasone. Hypothalamic neuron\u2013specific\n                    <jats:italic>Dnmt3a<\/jats:italic>\n                    -deficient mice exhibited upregulation of\n                    <jats:italic>Agtr1a<\/jats:italic>\n                    in the PVN and salt-induced BP elevation without dexamethasone treatment. By contrast, dexamethasone-treated\n                    <jats:italic>Agtr1a<\/jats:italic>\n                    -deficient mice failed to show salt-induced BP elevation, despite reduced expression of\n                    <jats:italic>Dnmt3a<\/jats:italic>\n                    . Thus, epigenetic modulation of hypothalamic angiotensin signaling contributes to salt-sensitive hypertension induced by prenatal glucocorticoid excess in offspring of mothers that are malnourished during pregnancy.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.95625","type":"journal-article","created":{"date-parts":[[2018,10,23]],"date-time":"2018-10-23T17:12:57Z","timestamp":1540314777000},"source":"Crossref","is-referenced-by-count":44,"title":["Aberrant DNA methylation of hypothalamic angiotensin receptor in prenatal programmed hypertension"],"prefix":"10.1172","volume":"3","author":[{"given":"Fumiko","family":"Kawakami-Mori","sequence":"first","affiliation":[{"name":"Division of Clinical Epigenetics, Research Center for Advanced Science and Technology (RCAST), The University of Tokyo, Tokyo, Japan."},{"name":"Division of Endocrinology, Mitsui Memorial Hospital, Tokyo, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9542-847X","authenticated-orcid":true,"given":"Mitsuhiro","family":"Nishimoto","sequence":"additional","affiliation":[{"name":"Division of Clinical Epigenetics, Research Center for Advanced Science and Technology (RCAST), The University of Tokyo, Tokyo, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Latapati","family":"Reheman","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, International University of Health and Welfare, School of Medicine, Narita Hospital IUHW, Tokyo, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wakako","family":"Kawarazaki","sequence":"additional","affiliation":[{"name":"Division of Clinical Epigenetics, Research Center for Advanced Science and Technology (RCAST), The University of Tokyo, Tokyo, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nobuhiro","family":"Ayuzawa","sequence":"additional","affiliation":[{"name":"Division of Clinical Epigenetics, Research Center for Advanced Science and Technology (RCAST), The University of Tokyo, Tokyo, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9411-1611","authenticated-orcid":true,"given":"Kohei","family":"Ueda","sequence":"additional","affiliation":[{"name":"Division of Clinical Epigenetics, Research Center for Advanced Science and Technology (RCAST), The University of Tokyo, Tokyo, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daigoro","family":"Hirohama","sequence":"additional","affiliation":[{"name":"Division of Clinical Epigenetics, Research Center for Advanced Science and Technology (RCAST), The University of Tokyo, Tokyo, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daisuke","family":"Kohno","sequence":"additional","affiliation":[{"name":"Advanced Scientific Research Leaders Development Unit, Gunma University, Gunma, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1680-1243","authenticated-orcid":true,"given":"Shigeyoshi","family":"Oba","sequence":"additional","affiliation":[{"name":"Division of Clinical Epigenetics, Research Center for Advanced Science and Technology (RCAST), The University of Tokyo, Tokyo, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8742-5129","authenticated-orcid":true,"given":"Tatsuo","family":"Shimosawa","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, International University of Health and Welfare, School of Medicine, Narita Hospital IUHW, Tokyo, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takeshi","family":"Marumo","sequence":"additional","affiliation":[{"name":"Division of Clinical Epigenetics, Research Center for Advanced Science and Technology (RCAST), The University of Tokyo, Tokyo, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshiro","family":"Fujita","sequence":"additional","affiliation":[{"name":"Division of Clinical Epigenetics, Research Center for Advanced Science and Technology (RCAST), The University of Tokyo, Tokyo, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"232","published-online":{"date-parts":[[2018,11,2]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.298.6673.564"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00029.2013"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/S0039-128X(96)00165-1"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2005030300"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.00309.2004"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1097\/HJH.0b013e328340aa18"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.116.08372"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1172\/JCI113709"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.107.091009"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1038\/nm.2337"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1007\/s00467-016-3359-8"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.113.02330"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.112.199356"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00123.2008"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1203\/01.PDR.0000127012.37315.36"},{"issue":"5 Pt 2","key":"B16","first-page":"R1178","article-title":"Role of paraventricular angiotensin AT1 receptors in salt-sensitive hypertension in mRen-2 transgenic rats","volume":"270","author":"Li","year":"1996","journal-title":"Am J Physiol"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3674-16.2017"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3806-12.2013"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1152\/physiolgenomics.00029.2016"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2826.1995.tb00714.x"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1038\/nrg3230"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1038\/ijo.2016.64"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1316-14.2014"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1177\/1933719109351935"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1038\/ng1598"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1038\/nature14248"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00744.2002"},{"key":"B28","doi-asserted-by":"crossref","DOI":"10.1186\/1741-7007-7-38","article-title":"Expression of the peroxisome proliferator activated receptor gamma gene is repressed by DNA methylation in visceral adipose tissue of mouse models of diabetes","volume":"7","author":"Fujiki","year":"2009","journal-title":"BMC Biol"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.00078.2015"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(09)60144-6"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.108.824730"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.110.161349"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.115.06736"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.115.06263"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1172\/JCI88641"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1016\/j.physbeh.2014.01.016"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1038\/nm.2372"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.116.305697"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0303-09.2010"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2012.01.060"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.116.07747"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20081188"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1038\/ijo.2016.64"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.117.08550"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1038\/nature02633"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2005.08.035"}],"container-title":["JCI Insight"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/insight.jci.org\/articles\/view\/95625\/files\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T12:38:47Z","timestamp":1779194327000},"score":1,"resource":{"primary":{"URL":"https:\/\/insight.jci.org\/articles\/view\/95625"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,11,2]]},"references-count":46,"journal-issue":{"issue":"21","published-online":{"date-parts":[[2018,11,2]]},"published-print":{"date-parts":[[2018,11,2]]}},"alternative-id":["10.1172\/jci.insight.95625"],"URL":"https:\/\/doi.org\/10.1172\/jci.insight.95625","relation":{},"ISSN":["2379-3708"],"issn-type":[{"value":"2379-3708","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,11,2]]},"article-number":"e95625"}}