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

Lenzini, Livia; Caroccia, Brasilina; Campos, Abril González; Fassina, Ambrogio; Belloni, Anna S.; Seccia, Teresa M.; Kuppusamy, Maniselvan; Ferraro, Silvia; Skander, Ghizlane; Bader, Michael; Rainey, William E.; Rossi, Gian Paolo

doi:10.1210/jc.2013-2900

Cited by 59Hormonal Regulation and HypertensionIon channel regulation and functionAdrenal and Paraganglionic Tumors

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

Lenzini, Livia, Caroccia, Brasilina, Campos, Abril González, Fassina, Ambrogio, Belloni, Anna S., Seccia, Teresa M., Kuppusamy, Maniselvan, Ferraro, Silvia +4 more·2014·The Journal of Clinical Endocrinology & Metabolism

DOI 10.1210/jc.2013-2900

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Abstract

Context The molecular mechanisms of primary aldosteronism, a common cause of human hypertension, are unknown, but alterations of K(+) channels can play a key role. Objective 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. Design 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. Results 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 Conclusions 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 activ…

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miR-23 can impact aldosterone production through the target gene TASK-2.
“One of the common causes of hypertension is primary aldosteronism, and miR-23 can impact aldosterone production through the target gene Twik associated acid sensitive K (+) channel 2 (TASK-2).”
From Recent advances of miR-23 in human diseases and growth development (2025) · cites this paper as [68]
High expression of miR-23 can lead to a decrease in TASK-2 activity, and then increase the expression of acute regulatory proteins and aldosterone synthase in steroid production.
“The high expression of miR-23 can lead to a decrease in TASK-2 activity, and then increase the expression of acute regulatory proteins and aldosterone synthase in steroid production [68].”
From Recent advances of miR-23 in human diseases and growth development (2025) · cites this paper as [68]

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Aldosterone-producing adenomas causing human primary aldosteronism are characterized by under-expression of the Twik-related acid-sensitive K+ channel 2 (Task-2) gene.
Lenzini, L., SECCIA, T. M., Caroccia, B., Skander, G., PESSINA, A. C., Rossi, G. P., Recarti, C., & MR, P. (2010) · Padua Research Archive (University of Padova)
Self-citation
The Twik-Related Acid-Sensitive K+ channel 2 (TASK-2) gene is under-expressed in aldosterone producing adenoma causing human primary aldosteronism.
Lenzini, L., SECCIA, T. M., Caroccia, B., Pozzan, T., Pelizzo, M. R., PESSINA, A. C., Belloni, A. S., Rossi, G. P., Recarti, C., Ceolotto, G., et al. (2011) · Padua Research Archive (University of Padova)
Self-citation
Under-expression of the TWIK-related acid-sensitive K+ channel 2 (TASK-2) gene is a hallmark of aldosterone producing adenoma causing human primary aldosteronism
Lenzini, L., Seccia, T. M., Caroccia, B., Recarti, C., Pelizzo, M. R., & Rossi, G. P. (2010) · Padua Research Archive (University of Padova) · Cited by 1 · see citing works
Self-citation
Under-Expression of the Twik-Related Acid-Sensitive K+ Channel 2 (TASK-2) Gene in Aldosterone-Producing Adenoma Causing Human Primary Aldosteronism
Rossi, G. P., Lenzini, L., SECCIA, T. M., Caroccia, B., Skander, G., PESSINA, A. C., Recarti, C., & MR, P. (2010) · Padua Research Archive (University of Padova)
Self-citation
Mutations of the Twik-Related Acid-Sensitive K+ Channel 2 Promoter in Human Primary Aldosteronism
Lenzini, L., Prisco, S., Gallina, M., Kuppusamy, M., & Rossi, G. P. (2017) · Endocrinology · doi:10.1210/en.2017-03119 · Cited by 8 · see citing works
Self-citation

Authors: Lenzini, L., Caroccia, B., Campos, A. G., Fassina, A., Belloni, A. S., Seccia, T. M., Kuppusamy, M., Ferraro, S., Skander, G., Bader, M., Rainey, W. E., & Rossi, G. P.
Affiliations: 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;
University of Padua (IT)
Max-Delbrück-Center for Molecular Medicine (M.B.), 13092 Berlin, Germany;
University of Michigan (US)
Corresponding author: Rossi, Gian Paolo
ORCID: Lenzini, Livia
Caroccia, Brasilina
Fassina, Ambrogio
Seccia, Teresa M.
Kuppusamy, Maniselvan
Rainey, William E.
Rossi, Gian Paolo
Venue: The Journal of Clinical Endocrinology & Metabolism
Publisher: The Endocrine Society
Published: 2014-04-01
Volume: 99
Issue: 4
Pages: E674-E682
ISSN: 0021-972X (ISSN-L)
1945-7197
DOI: 10.1210/jc.2013-2900
OpenAlex: W1987591029
Cited by: 59
References: 39
Citations by year: 2026: 2 · 2025: 1 · 2024: 1 · 2023: 2 · 2022: 3 · 2021: 4 · 2020: 5 · 2019: 5 · 2018: 7 · 2017: 7 · 2016: 5 · 2015: 9 · 2014: 8
FWCI: 5.77
Type: journal article
Language: en
Open access: closed
Locations: The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
PubMed (publishedVersion)
Padua Research Archive (University of Padova) (submittedVersion)
Topics: Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal Regulation and Hypertension
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion channel regulation and function
Health Sciences › Medicine › Surgery › Adrenal and Paraganglionic Tumors
Keywords: TASK-2, primary aldosteronism, aldosterone-producing adenoma, microRNA regulation, miR-23, miR-34, CYP11B2, steroidogenic acute regulatory protein, aldosterone biosynthesis, dominant negative mutation, 3' untranslated region, adrenal cortex, hypertension, hypokalemia
MeSH terms: Adenoma, Adrenal Cortex Neoplasms, Aldosterone, Cells, Cultured, Humans, Hyperaldosteronism, Paraneoplastic Endocrine Syndromes, Down-Regulation, Gene Expression Regulation, Neoplastic, Gene Expression Profiling, Potassium Channels, Tandem Pore Domain, Microarray Analysis, HEK293 Cells

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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

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