{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T15:36:46Z","timestamp":1791041806970,"version":"4.1.0"},"reference-count":54,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"2","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Hypertension"],"published-print":{"date-parts":[[2023,2]]},"abstract":"<jats:sec>\n            <jats:title>Background:<\/jats:title>\n            <jats:p>\n              Aldosterone-producing adenomas (APAs) are a major cause of primary aldosteronism, a condition of low-renin hypertension, in which aldosterone overproduction is usually driven by a somatic activating mutation in an ion pump or channel.\n              <jats:italic toggle=\"yes\">TSPAN12<\/jats:italic>\n              is differentially expressed in different subgroups of APAs suggesting a role in APA pathophysiology. Our objective was to determine the function of TSPAN12 (tetraspanin 12) in adrenal physiology and pathophysiology.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods:<\/jats:title>\n            <jats:p>APA specimens, pig adrenals under dietary sodium modulation, and a human adrenocortical cell line HAC15 were used for functional characterization of TSPAN12 in vivo and in vitro.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results:<\/jats:title>\n            <jats:p>\n              Gene ontology analysis of 21 APA transcriptomes dichotomized according to high versus low\n              <jats:italic toggle=\"yes\">TSPAN12<\/jats:italic>\n              transcript levels highlighted a function for\n              <jats:italic toggle=\"yes\">TSPAN12<\/jats:italic>\n              related to the renin-angiotensin system.\n              <jats:italic toggle=\"yes\">TSPAN12<\/jats:italic>\n              expression levels in a cohort of 30 APAs were inversely correlated with baseline plasma aldosterone concentrations (\n              <jats:italic toggle=\"yes\">R<\/jats:italic>\n              =\u22120.47;\n              <jats:italic toggle=\"yes\">P<\/jats:italic>\n              =0.009). In a pig model of renin-angiotensin system activation by dietary salt restriction,\n              <jats:italic toggle=\"yes\">TSPAN12<\/jats:italic>\n              mRNA levels and TSPAN12 immunostaining were markedly increased in the zona glomerulosa layer of the adrenal cortex. In vitro stimulation of human adrenocortical human adrenocortical cells with 10 nM angiotensin II for 6 hours caused a 1.6-fold\u00b10.13 increase in\n              <jats:italic toggle=\"yes\">TSPAN12<\/jats:italic>\n              expression, which was ablated by 10 \u03bcM nifedipine (\n              <jats:italic toggle=\"yes\">P<\/jats:italic>\n              =0.0097) or 30 \u03bcM W-7 (\n              <jats:italic toggle=\"yes\">P<\/jats:italic>\n              =0.0022). Gene silencing of\n              <jats:italic toggle=\"yes\">TSPAN12<\/jats:italic>\n              in human adrenocortical cells demonstrated its inverse effect on aldosterone secretion under basal and angiotensin II stimulated conditions.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions:<\/jats:title>\n            <jats:p>Our findings show that TSPAN12 is a negative regulator of aldosterone production and could contribute to aldosterone overproduction in primary aldosteronism.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/hypertensionaha.122.19783","type":"journal-article","created":{"date-parts":[[2022,12,2]],"date-time":"2022-12-02T10:03:40Z","timestamp":1669975420000},"page":"440-450","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":4,"title":["TSPAN12 (Tetraspanin 12) Is a Novel Negative Regulator of Aldosterone Production in Adrenal Physiology and Aldosterone-Producing Adenomas"],"prefix":"10.1161","volume":"80","author":[{"given":"Siyuan","family":"Gong","sequence":"first","affiliation":[{"name":"Medizinische Klinik und Poliklinik IV, Klinikum der Universit\u00e4t M\u00fcnchen, LMU M\u00fcnchen, Germany (S.G., M.T., M.B., M.R., T.A.W.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martina","family":"Tetti","sequence":"additional","affiliation":[{"name":"Medizinische Klinik und Poliklinik IV, Klinikum der Universit\u00e4t M\u00fcnchen, LMU M\u00fcnchen, Germany (S.G., M.T., M.B., M.R., T.A.W.)."},{"name":"Division of Internal Medicine and Hypertension, Department of Medical Sciences, University of Turin, Italy (M.T., P.M., T.A.W.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7785-7502","authenticated-orcid":true,"given":"Elisabeth","family":"Kemter","sequence":"additional","affiliation":[{"name":"Chair for Molecular Animal Breeding and Biotechnology, Gene Center and Department of Veterinary Sciences, Ludwig-Maximilians-Universit\u00e4t M\u00fcnchen, Munich, Germany (E.K., E.W.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mirko","family":"Peitzsch","sequence":"additional","affiliation":[{"name":"Institute of Clinical Chemistry and Laboratory Medicine, University Hospital and Faculty of Medicine Carl Gustav Carus, Technische Universit\u00e4t Dresden, Germany (M.P., G.E.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5480-1116","authenticated-orcid":true,"given":"Paolo","family":"Mulatero","sequence":"additional","affiliation":[{"name":"Division of Internal Medicine and Hypertension, Department of Medical Sciences, University of Turin, Italy (M.T., P.M., T.A.W.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Bidlingmaier","sequence":"additional","affiliation":[{"name":"Medizinische Klinik und Poliklinik IV, Klinikum der Universit\u00e4t M\u00fcnchen, LMU M\u00fcnchen, Germany (S.G., M.T., M.B., M.R., T.A.W.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Graeme","family":"Eisenhofer","sequence":"additional","affiliation":[{"name":"Institute of Clinical Chemistry and Laboratory Medicine, University Hospital and Faculty of Medicine Carl Gustav Carus, Technische Universit\u00e4t Dresden, Germany (M.P., G.E.)."},{"name":"Department of Medicine III, University Hospital Carl Gustav Carus, Technische Universit\u00e4t Dresden, Germany (G.E.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0430-9510","authenticated-orcid":true,"given":"Eckhard","family":"Wolf","sequence":"additional","affiliation":[{"name":"Chair for Molecular Animal Breeding and Biotechnology, Gene Center and Department of Veterinary Sciences, Ludwig-Maximilians-Universit\u00e4t M\u00fcnchen, Munich, Germany (E.K., E.W.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9817-9875","authenticated-orcid":true,"given":"Martin","family":"Reincke","sequence":"additional","affiliation":[{"name":"Medizinische Klinik und Poliklinik IV, Klinikum der Universit\u00e4t M\u00fcnchen, LMU M\u00fcnchen, Germany (S.G., M.T., M.B., M.R., T.A.W.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2388-6444","authenticated-orcid":true,"given":"Tracy Ann","family":"Williams","sequence":"additional","affiliation":[{"name":"Medizinische Klinik und Poliklinik IV, Klinikum der Universit\u00e4t M\u00fcnchen, LMU M\u00fcnchen, Germany (S.G., M.T., M.B., M.R., T.A.W.)."},{"name":"Division of Internal Medicine and Hypertension, Department of Medical Sciences, University of Turin, Italy (M.T., P.M., 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