{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T16:02:16Z","timestamp":1791820936189,"version":"4.3.4"},"reference-count":40,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"5","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Hypertension"],"published-print":{"date-parts":[[2015,5]]},"abstract":"<jats:p>\n            Common somatic mutations in\n            <jats:italic>CACNAID<\/jats:italic>\n            and\n            <jats:italic>ATP1A1<\/jats:italic>\n            may define a subgroup of smaller, zona glomerulosa (ZG)\u2013like aldosterone-producing adenomas. We have therefore sought signature ZG genes, which may provide insight into the frequency and pathogenesis of ZG-like aldosterone-producing adenomas. Twenty-one pairs of zona fasciculata and ZG and 14 paired aldosterone-producing adenomas from 14 patients with Conn\u2019s syndrome and 7 patients with pheochromocytoma were assayed by the Affymetrix Human Genome U133 Plus 2.0 Array. Validation by quantitative real-time polymerase chain reaction was performed on genes &gt;10-fold upregulated in ZG (compared with zona fasciculata) and &gt;10-fold upregulated in aldosterone-producing adenomas (compared with ZG).\n            <jats:italic>DACH1<\/jats:italic>\n            , a gene associated with tumor progression, was further analyzed. The role of\n            <jats:italic>DACH1<\/jats:italic>\n            on steroidogenesis, transforming growth factor-\u03b2, and Wnt signaling activity was assessed in the human adrenocortical cell line, H295R. Immunohistochemistry confirmed selective expression of DACH1 in human ZG. Silencing of\n            <jats:italic>DACH1<\/jats:italic>\n            in H295R cells increased\n            <jats:italic>CYP11B2<\/jats:italic>\n            mRNA levels and aldosterone production, whereas overexpression of\n            <jats:italic>DACH1<\/jats:italic>\n            decreased aldosterone production. Overexpression of\n            <jats:italic>DACH1<\/jats:italic>\n            in H295R cells activated the transforming growth factor-\u03b2 and canonical Wnt signaling pathways but inhibited the noncanonical Wnt signaling pathway. Stimulation of primary human adrenal cells with angiotensin II decreased\n            <jats:italic>DACH1<\/jats:italic>\n            mRNA expression. Interestingly, there was little overlap between our top ZG genes and those in rodent ZG. In conclusion, (1) the transcriptome profile of human ZG differs from rodent ZG, (2)\n            <jats:italic>DACH1<\/jats:italic>\n            inhibits aldosterone secretion in human adrenals, and (3) transforming growth factor-\u03b2 signaling pathway is activated in\n            <jats:italic>DACH1<\/jats:italic>\n            overexpressed cells and may mediate inhibition of aldosterone secretion in human adrenals.\n          <\/jats:p>","DOI":"10.1161\/hyp.0000000000000025","type":"journal-article","created":{"date-parts":[[2015,3,17]],"date-time":"2015-03-17T03:06:32Z","timestamp":1426561592000},"page":"1103-1110","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":28,"title":["<i>DACH1<\/i>\n            , a Zona Glomerulosa Selective Gene in the Human Adrenal, Activates Transforming Growth Factor-\u03b2 Signaling and Suppresses Aldosterone Secretion"],"prefix":"10.1161","volume":"65","author":[{"given":"Junhua","family":"Zhou","sequence":"first","affiliation":[{"name":"From the Clinical Pharmacology Unit, Department of Medicine (J.Z., L.H.S., C.A.B., C.M., A.E.D.T, E.A.B.A., M.J.B.), Cardiovascular Division, Department of Medicine (N.F.), University of Cambridge, Addenbrooke\u2019s Hospital, Cambridge, United Kingdom; Department of Clinical Biochemistry, GenomicsCoreLab, Cambridge NIHR BRC, Department of Clinical Biochemistry (S.G.N., I.M.), and Human Research Tissue Bank, Cambridge University Hospitals NHS Foundation Trust (W.Z.), Addenbrooke\u2019s Hospital, Cambridge,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lalarukh Haris","family":"Shaikh","sequence":"additional","affiliation":[{"name":"From the Clinical Pharmacology Unit, Department of Medicine (J.Z., L.H.S., C.A.B., C.M., A.E.D.T, E.A.B.A., M.J.B.), Cardiovascular Division, Department of Medicine (N.F.), University of Cambridge, Addenbrooke\u2019s Hospital, Cambridge, United Kingdom; Department of Clinical Biochemistry, GenomicsCoreLab, Cambridge NIHR BRC, Department of Clinical Biochemistry (S.G.N., I.M.), and Human Research Tissue Bank, Cambridge University Hospitals NHS Foundation Trust (W.Z.), Addenbrooke\u2019s Hospital, Cambridge,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sudeshna G.","family":"Neogi","sequence":"additional","affiliation":[{"name":"From the Clinical Pharmacology Unit, Department of Medicine (J.Z., L.H.S., C.A.B., C.M., A.E.D.T, E.A.B.A., M.J.B.), Cardiovascular Division, Department of Medicine (N.F.), University of Cambridge, Addenbrooke\u2019s Hospital, Cambridge, United Kingdom; Department of Clinical Biochemistry, GenomicsCoreLab, Cambridge NIHR BRC, Department of Clinical Biochemistry (S.G.N., I.M.), and Human Research Tissue Bank, Cambridge University Hospitals NHS Foundation Trust (W.Z.), Addenbrooke\u2019s Hospital, Cambridge,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian","family":"McFarlane","sequence":"additional","affiliation":[{"name":"From the Clinical Pharmacology Unit, Department of Medicine (J.Z., L.H.S., C.A.B., C.M., A.E.D.T, E.A.B.A., M.J.B.), Cardiovascular Division, Department of Medicine (N.F.), University of Cambridge, Addenbrooke\u2019s Hospital, Cambridge, United Kingdom; Department of Clinical Biochemistry, GenomicsCoreLab, Cambridge NIHR BRC, Department of Clinical Biochemistry (S.G.N., I.M.), and Human Research Tissue Bank, Cambridge University Hospitals NHS Foundation Trust (W.Z.), Addenbrooke\u2019s Hospital, Cambridge,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wanfeng","family":"Zhao","sequence":"additional","affiliation":[{"name":"From the Clinical Pharmacology Unit, Department of Medicine (J.Z., L.H.S., C.A.B., C.M., A.E.D.T, E.A.B.A., M.J.B.), Cardiovascular Division, Department of Medicine (N.F.), University of Cambridge, Addenbrooke\u2019s Hospital, Cambridge, United Kingdom; Department of Clinical Biochemistry, GenomicsCoreLab, Cambridge NIHR BRC, Department of Clinical Biochemistry (S.G.N., I.M.), and Human Research Tissue Bank, Cambridge University Hospitals NHS Foundation Trust (W.Z.), Addenbrooke\u2019s Hospital, Cambridge,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nichola","family":"Figg","sequence":"additional","affiliation":[{"name":"From the Clinical Pharmacology Unit, Department of Medicine (J.Z., L.H.S., C.A.B., C.M., A.E.D.T, E.A.B.A., M.J.B.), Cardiovascular Division, Department of Medicine (N.F.), University of Cambridge, Addenbrooke\u2019s Hospital, Cambridge, United Kingdom; Department of Clinical Biochemistry, GenomicsCoreLab, Cambridge NIHR BRC, Department of Clinical Biochemistry (S.G.N., I.M.), and Human Research Tissue Bank, Cambridge University Hospitals NHS Foundation Trust (W.Z.), Addenbrooke\u2019s Hospital, Cambridge,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheryl A.","family":"Brighton","sequence":"additional","affiliation":[{"name":"From the Clinical Pharmacology Unit, Department of Medicine (J.Z., L.H.S., C.A.B., C.M., A.E.D.T, E.A.B.A., M.J.B.), Cardiovascular Division, Department of Medicine (N.F.), University of Cambridge, Addenbrooke\u2019s Hospital, Cambridge, United Kingdom; Department of Clinical Biochemistry, GenomicsCoreLab, Cambridge NIHR BRC, Department of Clinical Biochemistry (S.G.N., I.M.), and Human Research Tissue Bank, Cambridge University Hospitals NHS Foundation Trust (W.Z.), Addenbrooke\u2019s Hospital, Cambridge,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmela","family":"Maniero","sequence":"additional","affiliation":[{"name":"From the Clinical Pharmacology Unit, Department of Medicine (J.Z., L.H.S., C.A.B., C.M., A.E.D.T, E.A.B.A., M.J.B.), Cardiovascular Division, Department of Medicine (N.F.), University of Cambridge, Addenbrooke\u2019s Hospital, Cambridge, United Kingdom; Department of Clinical Biochemistry, GenomicsCoreLab, Cambridge NIHR BRC, Department of Clinical Biochemistry (S.G.N., I.M.), and Human Research Tissue Bank, Cambridge University Hospitals NHS Foundation Trust (W.Z.), Addenbrooke\u2019s Hospital, Cambridge,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ada E.D.","family":"Teo","sequence":"additional","affiliation":[{"name":"From the Clinical Pharmacology Unit, Department of Medicine (J.Z., L.H.S., C.A.B., C.M., A.E.D.T, E.A.B.A., M.J.B.), Cardiovascular Division, Department of Medicine (N.F.), University of Cambridge, Addenbrooke\u2019s Hospital, Cambridge, United Kingdom; Department of Clinical Biochemistry, GenomicsCoreLab, Cambridge NIHR BRC, Department of Clinical Biochemistry (S.G.N., I.M.), and Human Research Tissue Bank, Cambridge University Hospitals NHS Foundation Trust (W.Z.), Addenbrooke\u2019s Hospital, Cambridge,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena A. B.","family":"Azizan","sequence":"additional","affiliation":[{"name":"From the Clinical Pharmacology Unit, Department of Medicine (J.Z., L.H.S., C.A.B., C.M., A.E.D.T, E.A.B.A., M.J.B.), Cardiovascular Division, Department of Medicine (N.F.), University of Cambridge, Addenbrooke\u2019s Hospital, Cambridge, United Kingdom; Department of Clinical Biochemistry, GenomicsCoreLab, Cambridge NIHR BRC, Department of Clinical Biochemistry (S.G.N., I.M.), and Human Research Tissue Bank, Cambridge University Hospitals NHS Foundation Trust (W.Z.), Addenbrooke\u2019s Hospital, Cambridge,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Morris J.","family":"Brown","sequence":"additional","affiliation":[{"name":"From the Clinical Pharmacology Unit, Department of Medicine (J.Z., L.H.S., C.A.B., C.M., A.E.D.T, E.A.B.A., M.J.B.), Cardiovascular Division, Department of Medicine (N.F.), University of Cambridge, Addenbrooke\u2019s Hospital, Cambridge, United Kingdom; Department of Clinical Biochemistry, GenomicsCoreLab, Cambridge NIHR BRC, Department of Clinical Biochemistry (S.G.N., I.M.), and Human Research Tissue Bank, Cambridge University Hospitals NHS Foundation Trust (W.Z.), Addenbrooke\u2019s Hospital, Cambridge,..."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_4_2_2","first-page":"3","article-title":"Presidential address. 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