Variants in striatin gene are associated with salt-sensitive blood pressure in mice and humans
Open accessAbstract
Striatin is a novel protein that interacts with steroid receptors and modifies rapid, nongenomic activity in vitro. We tested the hypothesis that striatin would in turn affect mineralocorticoid receptor function and consequently sodium, water, and blood pressure homeostasis in an animal model. We evaluated salt sensitivity of blood pressure in novel striatin heterozygote knockout mice. Compared with wild type, striatin heterozygote exhibited a significant increase in blood pressure when sodium intake was increased from restricted (0.03%) to liberal (1.6%) sodium. Furthermore, renal expression of mineralocorticoid receptor and its genomic downstream targets serum/glucocorticoid-regulated kinase 1, and epithelial sodium channel was increased in striatin heterozygote versus wild-type mice on liberal sodium intake while the pAkt/Akt ratio, readout of mineralocorticoid receptor's rapid, nongenomic pathway, was reduced. To determine the potential clinical relevance of these findings, we tested the association between single nucleotide polymorphic variants of striatin gene and salt sensitivity of blood pressure in 366 white hypertensive subjects. HapMap-derived tagging single nucleotide polymorphisms identified an association of rs2540923 with salt sensitivity of blood pressure (odds ratio, 6.25; 95% confidence interval, 1.7-20; P=0.01). These data provide the first in vivo evidence in humans and rodents that associates striatin with markers of mineralocorticoid receptor activity. The data also support the hypothesis that the rapid, nongenomic mineralocorticoid receptor pathway (mediated via striatin) has a role in modulating the interaction between salt intake and blood pressure.
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On liberal salt intake, STRN-deficient mice show increased expression of the mineralocorticoid receptor and several MR target genes, including ENaC and SGK1.
“On liberal salt intake, an increased expression of the mineralocorticoid receptor (MR) and several MR target genes (e.g. the epithelial sodium channel ENaC and the SGK1 kinase) was observed [97].”
From Physiologic functions of PP2A: Lessons from genetically modified mice (2019) · cites this paper as [97]
Compared with wild-type, STRN-deficient mice show enhanced salt sensitivity of blood pressure, with a higher increase upon liberal salt intake and a higher decrease upon salt restriction.
“Compared with WT mice, STRN-deficient mice showed an enhanced salt sensitivity of their blood pressure (BP), characterized by a higher increase in BP upon liberal salt intake, and a higher decrease in BP upon salt restriction.”
From Physiologic functions of PP2A: Lessons from genetically modified mice (2019) · cites this paper as [97]
In heterozygous STRN mice, STRN expression is decreased by about 50% in heart, kidney, adrenal gland, and aorta.
“In the heterozygous mice, decreased STRN expression by ~50% was confirmed in heart, kidney, adrenal gland and aorta.”
From Physiologic functions of PP2A: Lessons from genetically modified mice (2019) · cites this paper as [97]
Homozygous Strn-/- mice are likely not viable.
“Homozygous Strn -/-mice are likely not viable [97].”
From Physiologic functions of PP2A: Lessons from genetically modified mice (2019) · cites this paper as [97]
Heterozygous mice for the PP2A B′′′ subunit STRN reveal a potential role for PP2A in the kidneys and blood pressure homeostasis.
“A potential role for PP2A in the kidneys and the regulation of blood pressure homeostasis was revealed in heterozygous mice for the PP2A B‴ subunit STRN [97,98].”
From Physiologic functions of PP2A: Lessons from genetically modified mice (2019) · cites this paper as [97]
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- Authors
- Garza, A. E., Rariy, C. M., Sun, B., Williams, J. S., Lasky-Su, J., Baudrand, R., Yao, T., Moize, B., Hafiz, W. M., Romero, J. R., Adler, G. K., Ferri, C., Hopkins, P. N., Pojoga, L. H., & Williams, G. H.
- Affiliations
- Brigham and Women's Hospital (US)
- From the Division of Endocrinology, Diabetes and Hypertension, Department of Medicine (A.E.G., C.M.R., B.S., J.S.W., R.B., T.Y., B.M., W.M.H., J.R.R., G.K.A., L.H.P., G.H.W.) and Channing Department of Network Medicine (J.L.-S.), Brigham and Women’s Hospital, Harvard Medical School, Boston, MA; Department of Endocrinology, School of Medicine, Pontificia Universidad Catolica De Chile, Santiago, Chile (R.B.); Division of Internal Medicine & Nephrology and School of Internal Medicine, University of...
- ORCID
- Venue
- Hypertension
- Published
- 2015-01
- Volume
- 65
- Issue
- 1
- Pages
- 211-217
- ISSN
- 0194-911X (ISSN-L)
- 1524-4563
- PMC
- PMC4617687
- OpenAlex
- W1964626513
- Cited by
- 51
- References
- 24
- Citations by year
- 2026: 2 · 2025: 5 · 2024: 4 · 2023: 6 · 2022: 2 · 2021: 4 · 2020: 4 · 2019: 6 · 2018: 9 · 2017: 5 · 2016: 1 · 2015: 3
- FWCI
- 2.41
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Hypertension (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Archivio Istituzionale della Ricerca - Università degli Studi dell Aquila (submittedVersion)
- Funders
- National Heart, Lung, and Blood Institute (R01HL086907, R01HL069208, R01HL104032, T32HL007609, P50HL055000, R01HL114765, R01HL096518, R01HL047651, R01HL094452, R01HL11476, K24HL103845)
- NIH Clinical Center
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal Regulation and Hypertension
- Health Sciences › Nursing › Nutrition and Dietetics › Sodium Intake and Health
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Renin-Angiotensin System Studies
- Keywords
- striatin, mineralocorticoid receptor, sodium intake, single nucleotide polymorphisms, epithelial sodium channel, Akt signaling, sodium homeostasis
- MeSH terms
- Animals, Blood Pressure, Calmodulin-Binding Proteins, Disease Models, Animal, Gene Expression Regulation, Genotype, Humans, Hypertension, Membrane Proteins, Nerve Tissue Proteins, Phenotype, RNA, Messenger, Sodium, Dietary, Blotting, Western, Signal Transduction, Polymerase Chain Reaction, Mice, Knockout, Mice
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