Cited by 15Hormonal Regulation and HypertensionAdrenal and Paraganglionic TumorsAdrenal Hormones and Disorders

Pre-B lymphocyte protein 3 (VPREB3) expression in the adrenal cortex: precedent for non-immunological roles in normal and neoplastic human tissues

Felizola, Saulo J. A., Katsu, Koshin, Ise, Kazue, Nakamura, Yasuhiro, Arai, Yoichi, Satoh, Fumitoshi, Sasano, Hironobu·2015·Endocrine Pathology

Abstract

The pre-B lymphocyte protein 3 (VPREB3) is expressed during B cell differentiation and in subsets of mature B lymphocytes and is mainly found in bone marrow and lymphoid tissue germinative centers. So far, its function in B cells remains to be clarified. The messenger RNA (mRNA) of VPREB3 was previously detected in aldosterone-producing adenomas (APA); however, further information about this protein in human adrenocortical cells and tissues is currently unavailable. Therefore, in the present study, we, for the first time, investigate the protein expression of VPREB3 in human adrenocortical tissues. In addition, we approach the previously suggested similarities in expression patterns of aldosterone-producing cells and Purkinje neurons. Immunohistochemical analysis of VPREB3 was performed in 13 nonpathological adrenals (NA), 6 adrenal glands with idiopathic hyperaldosteronism (IHA), 18 APA, 5 cortisol-producing adenomas (CPA), and 5 nonpathological human cerebellum specimens. The mRNA levels of VPREB3, steroidogenic enzymes, and other aldosterone biosynthesis markers were detected in 53 APA samples using real-time RT-PCR (qPCR) and compared to the clinical data of APA patients. In our results, the VPREB3 protein was diffusely detected in APA, partially or weakly detected in CPA, and immunolocalized in the zona glomerulosa of NA and IHA, as well as in the cytoplasm of cerebellar Purkinje cells. In APA, VPREB3 mRNA levels were significantly correlated to plasma aldosterone (P = 0.026; R = 0.30), KCNJ5 mutations (P = 0.0061; mutated 34:19 wild type), CYP11B2 (P < 0.0001; R = 0.65), Purkinje cell protein 4 (PCP4; P < 0.0001; R = 0.53), and voltage-dependent calcium channels CaV1.3 (P = 0.023; R = 0.31) and CaV3.2 (P = 0.0019; R = 0.42). Based on our data, we hypothesize a possible role for VPREB3 in aldosterone biosynthesis, and present ideas for future functional studies.

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Crossref · 10.1007/s12022-015-9366-7

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  • KCNJ5 mutations have been documented in approximately 40% of patients with aldosterone-producing adenomas from European cohorts, with much higher rates reported in patients from Japan and Asia.

    “Mutations in KCNJ5 (potassium channel) have been documented in patients with aldosterone-producing adenomas in approximately 40% of patients (151) from European cohorts, though much higher rates are reported in patients from Japan and Asia (152,153).”

    From Adrenal incidentaloma (2020) · cites this paper as [153]

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  • Adrenal incidentaloma

    Sherlock, M., Scarsbrook, A., Abbas, A., Fraser, S., Limumpornpetch, P., Dineen, R., & Stewart, P. M. (2020) · Endocrine Reviews · doi:10.1210/endrev/bnaa008 · Cited by 347 · see citing works

    “Mutations in KCNJ5 , CACNA1H , ATP1A1 , ATP2B3 , and CACNA1D account for approximately 50% of aldosterone-producing adrenal adenomas (159) in patients from Europe; this is likely to be higher in Asian patients.”
    Background

Authors
Felizola, S. J. A., Katsu, K., Ise, K., Nakamura, Y., Arai, Y., Satoh, F., & Sasano, H.
Affiliations
  • Tohoku University (JP)
  • Tohoku University Hospital (JP)
Corresponding author
Felizola, Saulo J. A.
Venue
Endocrine Pathology
Published
2015-04-10
Volume
26
Issue
2
Pages
119-128
ISSN
  • 1046-3976 (ISSN-L)
  • 1559-0097
OpenAlex
W1991812866
Cited by
15
References
36
Citations by year
2025: 2 · 2023: 3 · 2022: 4 · 2021: 2 · 2020: 1 · 2017: 2 · 2016: 1
FWCI
0.87
Type
journal article
Language
en
Open access
closed
Locations
  • Endocrine Pathology (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal Regulation and Hypertension
  • Health Sciences › Medicine › Surgery › Adrenal and Paraganglionic Tumors
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
Keywords
adrenal cortex, aldosterone-producing adenoma, idiopathic hyperaldosteronism, cortisol-producing adenoma, Purkinje cells, KCNJ5 mutation, CYP11B2, voltage-gated calcium channels, Cav1.3, Cav3.2, B cell differentiation
MeSH terms
Adenoma, Adrenal Cortex, Adrenal Cortex Neoplasms, Aldosterone, Angiotensin II, Humans, Mutation, Tumor Cells, Cultured, Gene Expression Regulation, Neoplastic, G Protein-Coupled Inwardly-Rectifying Potassium Channels, Metabolic Networks and Pathways, Pre-B Cell Receptors

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