Vitamin D receptor, an important transcription factor associated with aldosterone-producing adenoma

Changlong Bi; Bo Li; Lili Du; Lishan Wang; Yingqi Zhang; Zhifeng Cheng; Aixia Zhai

doi:10.1371/journal.pone.0082309

Vitamin D receptor, an important transcription factor associated with aldosterone-producing adenoma

PLoS One. 2013 Dec 20;8(12):e82309. doi: 10.1371/journal.pone.0082309. eCollection 2013.

Authors

Changlong Bi¹, Bo Li¹, Lili Du¹, Lishan Wang², Yingqi Zhang¹, Zhifeng Cheng¹, Aixia Zhai³

Affiliations

¹ Department of Endocrinology, Fourth Affiliated Hospital of Harbin Medical University, Harbin, China.
² FengHe (ShangHai) Information Technology Co., Ltd., Shanghai, China ; Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiao Tong University, Shanghai ,China.
³ Department of Microbiology, Harbin Medical University, Harbin, China ; Heilongjiang Provincial Science and Technology Innovation Team in Higher Education Institutes for Infection and Immunity, Harbin Medical University, Harbin , China ; Heilongjiang Provincial Key Laboratory for Infection and Immunity, Harbin Medical University, Harbin, China.

Abstract

Objective: To explore the endocrine mechanisms of aldosterone-producing adenoma (APA) by using the microarray expression profiles of normal and APA samples.

Methods: The gene expression profile GSE8514 was downloaded from Gene Expression Omnibus database, including samples from normal adrenals (n = 5) and APAs (n = 10). The differentially expressed genes (DEGs) were identified by samr package and endocrine DEGs were obtained according to Clinical Genome Database. Then, functional enrichment analysis of screened DEGs was performed by DAVID (Database for Annotation, Visualization and Integrated Discovery). Finally, a regulatory network was constructed to screen endocrine genes related with adrenal dysfunction and pathway enrichment analysis for the constructed network was performed.

Results: A total of 2149 DEGs were identified including 379 up- and 1770 down-regulated genes. And 26 endocrine genes were filtered from the DEGs. Furthermore, the down-regulated DEGs are mainly related to protein kinase cascade, response to molecule of bacterial origin, response to lipopolysaccharide, cellular macromolecule catabolic process and macromolecule catabolic process, while the up-regulated DEGs are related with regulation of ion transport. The target genes of VDR (vitamin D receptor), one of the three endocrine genes differentially expressed in the regulatory network, were endocrine genes including CYP24A1 (25-hydroxyvitamin D-24-hydroxylase) and PTH (parathyroid hormone). Three pathways may be associated with APA pathogenesis including cytokine-cytokine receptor interaction, pathways in cancer and autoimmune thyroid disease.

Conclusion: The VDR is the most significant transcription factor and related endocrine genes might play important roles in the endocrine mechanisms of APA.

Publication types

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

MeSH terms

Adenoma / genetics*
Adrenal Gland Neoplasms / genetics*
Adult
Aldosterone / biosynthesis*
Cluster Analysis
Down-Regulation / genetics
Gene Expression Regulation, Neoplastic
Gene Ontology
Gene Regulatory Networks
Humans
Receptors, Calcitriol / genetics*
Transcriptome
Up-Regulation / genetics

Substances

Receptors, Calcitriol
Aldosterone

Grants and funding

This work was funded by grants from the Foundation of Heilongjiang Provincial Education Department of China (12531319, 11551238), Foundation of Heilongjiang Provincial Health Department of China (2009-181, 2009-207, 2012-715), and Foundation of Heilongjiang Provincial Postdoctor of China (LBH-Z11086). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.