{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T17:12:00Z","timestamp":1790615520288,"version":"4.1.0"},"reference-count":38,"publisher":"The Endocrine Society","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2014,4,1]]},"abstract":"<jats:sec><jats:title>Context:<\/jats:title><jats:p>The molecular mechanisms of primary aldosteronism, a common cause of human hypertension, are unknown, but alterations of K+ channels can play a key role.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective:<\/jats:title><jats:p>The objective of the study was to investigate the following: 1) the expression of the Twik-related acid-sensitive K+ channels (TASK) in aldosterone producing adenomas (APAs); 2) the role of TASK-2 in aldosterone synthesis; and 3) the determinants of TASK-2-blunted expression in APAs.<\/jats:p><\/jats:sec><jats:sec><jats:title>Design:<\/jats:title><jats:p>We analyzed the transcriptome and the microRNA profiles of 32 consecutive APAs and investigated the protein expression and localization of TASK-2 in APA and adrenocortical cell lines (H295R and HAC15) using immunoblotting and confocal microscopy. The functional effect of TASK-2 blunted activity caused by a dominant-negative mutation on steroidogenic enzymes, and aldosterone production was also assessed. TASK-2 regulation by selected microRNA was studied by a luciferase assay.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results:<\/jats:title><jats:p>TASK-2 was consistently less expressed at the transcript and protein levels in APAs than in the normal human adrenal cortex. H295R cell transfection with a TASK-2 dominant-negative mutant construct significantly increased the aldosterone production by 153% and the gene expression of aldosterone synthase (CYP11B2, gene expression fold change 3.1 vs control, P &amp;lt; .05) and the steroidogenic acute regulatory protein (gene expression fold change 1.8 vs control, P &amp;lt; .05). Two microRNAs, hsa-miR-23 and hsa-miR-34, were found to decrease the TASK-2 expression by binding to the 3\u2032 untranslated region of the TASK-2 gene.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions:<\/jats:title><jats:p>The TASK-2 channel lower expression represents a hallmark of APA and is associated with a higher expression of hsa-miR-23 and hsa-miR-34. The ensuing blunted TASK-2 activity increased the production of aldosterone in vitro and the expression of steroidogenic acute regulatory protein and CYP11B2. Hence, the lower expression of TASK-2 channel in APA cells can explain high aldosterone secretion in human primary aldosteronism despite the suppression of angiotensin II, hypertension, and hypokalemia.<\/jats:p><\/jats:sec>","DOI":"10.1210\/jc.2013-2900","type":"journal-article","created":{"date-parts":[[2013,11,28]],"date-time":"2013-11-28T04:25:49Z","timestamp":1385612749000},"page":"E674-E682","source":"Crossref","is-referenced-by-count":48,"title":["Lower Expression of the TWIK-Related Acid-Sensitive K+ Channel 2 (TASK-2) Gene Is a Hallmark of Aldosterone-Producing Adenoma Causing Human Primary Aldosteronism"],"prefix":"10.1210","volume":"99","author":[{"given":"Livia","family":"Lenzini","sequence":"first","affiliation":[{"name":"Internal Medicine 4 (L.L., B.C., A.G.C., T.M.S., M.K., S.F., G.S., G.P.R.), 35128 Padua, Italy;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brasilina","family":"Caroccia","sequence":"first","affiliation":[{"name":"Internal Medicine 4 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