Regulation of 11β-hydroxysteroid dehydrogenase type 2 by microRNA.

Rezaei, Mina; Andrieu, Thomas; Neuenschwander, Samuel; Bruggmann, Rémy; Mordasini, David; Frey, Felix J; Vogt, Bruno; Frey, Brigitte M. (2014). Regulation of 11β-hydroxysteroid dehydrogenase type 2 by microRNA. Hypertension, 64(4), pp. 860-866. American Heart Association 10.1161/HYPERTENSIONAHA.114.00002

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The enzyme 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2) is selectively expressed in aldosterone target tissues, conferring aldosterone selectivity for the mineralocorticoid receptor. A diminished activity causes salt-sensitive hypertension. The mechanism of the variable and distinct 11β-hydroxysteroid dehydrogenase type 2 gene (HSD11B2) expression in the cortical collecting duct is poorly understood. Here, we analyzed for the first time whether the 11β-HSD2 expression is modulated by microRNAs (miRNAs). In silico analysis revealed 53 and 27 miRNAs with potential binding sites on human or rat HSD11B2 3'-untranslated region. A reporter assay demonstrated 3'-untranslated region-dependent regulation of human and rodent HSD11B2. miRNAs were profiled from cortical collecting ducts and proximal convoluted tubules. Bioinformatic analyses showed a distinct clustering for cortical collecting ducts and proximal convoluted tubules with 53 of 375 miRNAs, where 13 were predicted to bind to the rat HSD11B2 3'-untranslated region. To gain insight into potentially relevant miRNAs in vivo, we investigated 2 models with differential 11β-HSD2 activity linked with salt-sensitive hypertension. (1) Comparing Sprague-Dawley with low and Wistar rats with high 11β-HSD2 activity revealed rno-miR-20a-5p, rno-miR-19b-3p, and rno-miR-190a-5p to be differentially expressed. (2) Uninephrectomy lowered 11β-HSD2 activity in the residual kidney with differentially expressed rno-miR-19b-3p, rno-miR-29b-3p, and rno-miR-26-5p. In conclusion, miRNA-dependent mechanisms seem to modulate 11β-HSD2 dosage in health and disease states.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > Unit Childrens Hospital > Forschungsgruppe Nephrologie / Hypertonie
04 Faculty of Medicine > Department of Dermatology, Urology, Rheumatology, Nephrology, Osteoporosis (DURN) > Clinic of Nephrology and Hypertension

UniBE Contributor:

Rezaei, Mina; Andrieu, Thomas; Neuenschwander, Samuel; Bruggmann, Rémy; Mordasini, David; Vogt, Bruno and Frey, Brigitte

Subjects:

600 Technology > 610 Medicine & health

ISSN:

1524-4563

Publisher:

American Heart Association

Language:

English

Submitter:

Brigitte Frey

Date Deposited:

31 Dec 2019 08:23

Last Modified:

31 Dec 2019 08:26

Publisher DOI:

10.1161/HYPERTENSIONAHA.114.00002

PubMed ID:

24980668

Uncontrolled Keywords:

hypertension kidney microRNAs mineralocorticoids

BORIS DOI:

10.7892/boris.68292

URI:

https://boris.unibe.ch/id/eprint/68292

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