DACH1, a zona glomerulosa selective gene in the human adrenal, activates transforming growth factor-β signaling and suppresses aldosterone secretion

Hypertension
Junhua ZhouMorris J Brown

Abstract

Common somatic mutations in CACNAID and ATP1A1 may define a subgroup of smaller, zona glomerulosa (ZG)-like aldosterone-producing adenomas. We have therefore sought signature ZG genes, which may provide insight into the frequency and pathogenesis of ZG-like aldosterone-producing adenomas. Twenty-one pairs of zona fasciculata and ZG and 14 paired aldosterone-producing adenomas from 14 patients with Conn's syndrome and 7 patients with pheochromocytoma were assayed by the Affymetrix Human Genome U133 Plus 2.0 Array. Validation by quantitative real-time polymerase chain reaction was performed on genes >10-fold upregulated in ZG (compared with zona fasciculata) and >10-fold upregulated in aldosterone-producing adenomas (compared with ZG). DACH1, a gene associated with tumor progression, was further analyzed. The role of DACH1 on steroidogenesis, transforming growth factor-β, and Wnt signaling activity was assessed in the human adrenocortical cell line, H295R. Immunohistochemistry confirmed selective expression of DACH1 in human ZG. Silencing of DACH1 in H295R cells increased CYP11B2 mRNA levels and aldosterone production, whereas overexpression of DACH1 decreased aldosterone production. Overexpression of DACH1 in H295R cells activat...Continue Reading

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Citations

Sep 24, 2015·The New England Journal of Medicine·Ada E D TeoMorris J Brown
Apr 22, 2015·Clinical Endocrinology·Morris J Brown
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Nov 20, 2016·Acta Physiologica·S Bandulik
Apr 22, 2016·Scientific Reports·Catherine B XieMorris J Brown
Sep 28, 2017·Hypertension·Teresa M SecciaGian Paolo Rossi

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Methods Mentioned

BETA
laser capture microdissection
Assay
exome sequencing
transfection

Software Mentioned

CellD

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