Expression of inflammation-related genes in aldosterone-producing adenomas with KCNJ5 mutation

Masanori Murakami; Takanobu Yoshimoto; Yujiro Nakano; Kyoichiro Tsuchiya; Isao Minami; Ryotaro Bouchi; Yasuhisa Fujii; Kazuhiko Nakabayashi; Koshi Hashimoto; Ken-Ichiro Hata; Kazunori Kihara; Yoshihiro Ogawa

doi:10.1016/j.bbrc.2016.06.007

Expression of inflammation-related genes in aldosterone-producing adenomas with KCNJ5 mutation

Biochem Biophys Res Commun. 2016 Aug 5;476(4):614-619. doi: 10.1016/j.bbrc.2016.06.007. Epub 2016 Jun 7.

Affiliations

¹ Department of Molecular Endocrinology and Metabolism, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo 113-8510, Japan.
² Department of Molecular Endocrinology and Metabolism, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo 113-8510, Japan. Electronic address: tyoshimoto.mem@tmd.ac.jp.
³ Department of Urology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo 113-8510, Japan.
⁴ Department of Maternal-Fetal Biology, National Research Institute for Child Health and Development, Tokyo 157-8535, Japan.
⁵ Department of Molecular Endocrinology and Metabolism, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo 113-8510, Japan; Department of Preemptive Medicine and Metabolism, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo 113-8510, Japan.
⁶ Department of Molecular Endocrinology and Metabolism, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo 113-8510, Japan; Japan Science and Technology Agency, CREST, AMED, Tokyo 102-0076, Japan.

PMID: 27282482
DOI: 10.1016/j.bbrc.2016.06.007

Abstract

Background: The adrenocortical cells have been shown to produce various inflammatory cytokines such as TNFα and IL-6, which could modulate steroidogenesis. However, the role of inflammatory cytokines in aldosterone-producing adenomas (APAs) is not fully understood. In the present study, we examined the relationships between mRNA expression levels of the inflammation-related genes and somatic mutations in APA tissues.

Methods: We evaluated mRNA expression levels of TNFA, IL6, and NFKB1 in APA tissues obtained from 44 Japanese APA patients.

Results: We revealed that mRNA expression patterns of the inflammation-related genes depended on a KCNJ5 somatic mutation. In addition, we showed that mRNA expression levels of the inflammation-related genes correlated with those of the steroidogenic enzyme CYP11B1 in the patients with APAs.

Conclusion: The present study documented for the first time the expression of inflammation-related genes in APAs and the correlation of their expression levels with the KCNJ5 mutation status and mRNA expression levels of steroidogenic enzymes, indicating the pathophysiological relevance of inflammation-related genes in APAs.

Keywords: APA; Adrenal tumor; Inflammatory cytokine; KCNJ5.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adrenal Cortex Neoplasms / genetics*
Adrenal Cortex Neoplasms / metabolism*
Adrenocortical Adenoma / genetics*
Adrenocortical Adenoma / metabolism*
Adult
Aged
Aldosterone / biosynthesis*
Cytokines / genetics
Female
G Protein-Coupled Inwardly-Rectifying Potassium Channels / genetics*
Gene Expression
Humans
Inflammation Mediators / metabolism
Interleukin-6 / genetics
Male
Middle Aged
Mutation*
NF-kappa B p50 Subunit / genetics
RNA, Messenger / genetics
RNA, Messenger / metabolism
RNA, Neoplasm / genetics
RNA, Neoplasm / metabolism
Steroid 11-beta-Hydroxylase / genetics
Tumor Necrosis Factor-alpha / genetics

Substances

Cytokines
G Protein-Coupled Inwardly-Rectifying Potassium Channels
IL6 protein, human
Inflammation Mediators
Interleukin-6
KCNJ5 protein, human
NF-kappa B p50 Subunit
NFKB1 protein, human
RNA, Messenger
RNA, Neoplasm
TNF protein, human
Tumor Necrosis Factor-alpha
Aldosterone
Steroid 11-beta-Hydroxylase