title: Regulation of 11β-hydroxysteroid dehydrogenase type 2 by microRNA.
abstract: 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.
authors: From the Department of Nephrology, Hypertension, and Clinical Pharmacology (M.R., T.A., D.M., F.J.F., B.V., B.M.F.) and Department of Biology and Bioinformatics (S.N., R.B.), University of Bern, Bern, Switzerland; Vital-IT, Swiss Institute of Bioinformatics, University of Lausanne, Lausanne, Switzerland (S.N.); and Department of Clinical Research, University Hospital Bern, Bern, Switzerland (B.M.F.).
authors: Mina
authors: M
authors: Rezaei
authors: From the Department of Nephrology, Hypertension, and Clinical Pharmacology (M.R., T.A., D.M., F.J.F., B.V., B.M.F.) and Department of Biology and Bioinformatics (S.N., R.B.), University of Bern, Bern, Switzerland; Vital-IT, Swiss Institute of Bioinformatics, University of Lausanne, Lausanne, Switzerland (S.N.); and Department of Clinical Research, University Hospital Bern, Bern, Switzerland (B.M.F.).
authors: Thomas
authors: T
authors: Andrieu
authors: From the Department of Nephrology, Hypertension, and Clinical Pharmacology (M.R., T.A., D.M., F.J.F., B.V., B.M.F.) and Department of Biology and Bioinformatics (S.N., R.B.), University of Bern, Bern, Switzerland; Vital-IT, Swiss Institute of Bioinformatics, University of Lausanne, Lausanne, Switzerland (S.N.); and Department of Clinical Research, University Hospital Bern, Bern, Switzerland (B.M.F.).
authors: Samuel
authors: S
authors: Neuenschwander
authors: From the Department of Nephrology, Hypertension, and Clinical Pharmacology (M.R., T.A., D.M., F.J.F., B.V., B.M.F.) and Department of Biology and Bioinformatics (S.N., R.B.), University of Bern, Bern, Switzerland; Vital-IT, Swiss Institute of Bioinformatics, University of Lausanne, Lausanne, Switzerland (S.N.); and Department of Clinical Research, University Hospital Bern, Bern, Switzerland (B.M.F.).
authors: Rémy
authors: R
authors: Bruggmann
authors: From the Department of Nephrology, Hypertension, and Clinical Pharmacology (M.R., T.A., D.M., F.J.F., B.V., B.M.F.) and Department of Biology and Bioinformatics (S.N., R.B.), University of Bern, Bern, Switzerland; Vital-IT, Swiss Institute of Bioinformatics, University of Lausanne, Lausanne, Switzerland (S.N.); and Department of Clinical Research, University Hospital Bern, Bern, Switzerland (B.M.F.).
authors: David
authors: D
authors: Mordasini
authors: From the Department of Nephrology, Hypertension, and Clinical Pharmacology (M.R., T.A., D.M., F.J.F., B.V., B.M.F.) and Department of Biology and Bioinformatics (S.N., R.B.), University of Bern, Bern, Switzerland; Vital-IT, Swiss Institute of Bioinformatics, University of Lausanne, Lausanne, Switzerland (S.N.); and Department of Clinical Research, University Hospital Bern, Bern, Switzerland (B.M.F.).
authors: Felix J
authors: FJ
authors: Frey
authors: From the Department of Nephrology, Hypertension, and Clinical Pharmacology (M.R., T.A., D.M., F.J.F., B.V., B.M.F.) and Department of Biology and Bioinformatics (S.N., R.B.), University of Bern, Bern, Switzerland; Vital-IT, Swiss Institute of Bioinformatics, University of Lausanne, Lausanne, Switzerland (S.N.); and Department of Clinical Research, University Hospital Bern, Bern, Switzerland (B.M.F.).
authors: Bruno
authors: B
authors: Vogt
authors: From the Department of Nephrology, Hypertension, and Clinical Pharmacology (M.R., T.A., D.M., F.J.F., B.V., B.M.F.) and Department of Biology and Bioinformatics (S.N., R.B.), University of Bern, Bern, Switzerland; Vital-IT, Swiss Institute of Bioinformatics, University of Lausanne, Lausanne, Switzerland (S.N.); and Department of Clinical Research, University Hospital Bern, Bern, Switzerland (B.M.F.) brigitte.frey@dkf.unibe.ch.
authors: Brigitte M
authors: BM
authors: Frey
mesh_terms: D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2 / Q000235:genetics*; D020413:3' Untranslated Regions / Q000235:genetics*; D000818:Animals; D045744:Cell Line, Tumor; D016000:Cluster Analysis; D020869:Gene Expression Profiling; D015971:Gene Expression Regulation, Enzymologic; D019073:HT29 Cells; D006801:Humans; D006973:Hypertension / Q000209:etiology / Q000235:genetics; D007672:Kidney Cortex / Q000378:metabolism; D007685:Kidney Tubules, Collecting / Q000378:metabolism; D008297:Male; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017673:Sodium Chloride, Dietary / Q000008:administration & dosage / Q000633:toxicity; D013045:Species Specificity
chemical_list: D020413:3' Untranslated Regions; D035683:MicroRNAs; D017673:Sodium Chloride, Dietary; D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2
keywords: hypertension; kidney; microRNAs; mineralocorticoids