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MiR-192-5p in the Kidney Protects Against the Development of Hypertension. Hypertension 2019 02;73(2):399-406

Date

01/01/2019

Pubmed ID

30595117

Pubmed Central ID

PMC6339564

DOI

10.1161/HYPERTENSIONAHA.118.11875

Scopus ID

2-s2.0-85059796489   3 Citations

Abstract

MicroRNA miR-192-5p is one of the most abundant microRNAs in the kidney and targets the mRNA for ATP1B1 (β1 subunit of Na/K-ATPase). Na/K-ATPase drives renal tubular reabsorption. We hypothesized that miR-192-5p in the kidney would protect against the development of hypertension. We found miR-192-5p levels were significantly lower in kidney biopsy specimens from patients with hypertension (n=8) or hypertensive nephrosclerosis (n=32) compared with levels in controls (n=10). Similarly, Dahl salt-sensitive (SS) rats showed a reduced abundance of miR-192-5p in the renal cortex compared with congenic SS.13 rats that had reduced salt sensitivity (n=9; P<0.05). Treatment with anti-miR-192-5p delivered through renal artery injection in uninephrectomized SS.13 rats exacerbated hypertension significantly. Mean arterial pressure on a 4% NaCl high-salt diet at day 14 post anti-miR-192-5p treatment was 16 mm Hg higher than in rats treated with scrambled anti-miR (n=8 and 6; P<0.05). Similarly, Mir192 knockout mice on the high-salt diet treated with Ang II (angiotensin II) for 14 days exhibited a mean arterial pressure 22 mm Hg higher than wild-type mice (n=9 and 5; P<0.05). Furthermore, protein levels of ATP1B1 were higher in Dahl SS rats than in SS.13 rats. Na/K-ATPase activity increased in the renal cortex of SS.13 rats 9 days posttreatment with anti-miR-192-5p compared with that of control anti-miR treated rats. Intrarenal knockdown of ATP1B1 attenuated hypertension in SS.13 rats with intrarenal knockdown of miR-192-5p. In conclusion, miR-192-5p in the kidney protects against the development of hypertension, which is mediated, at least in part, by targeting Atp1b1.

Author List

Baker MA, Wang F, Liu Y, Kriegel AJ, Geurts AM, Usa K, Xue H, Wang D, Kong Y, Liang M

Authors

Aron Geurts PhD Associate Professor in the Physiology department at Medical College of Wisconsin
Mingyu Liang PhD Center Director, Professor in the Physiology department at Medical College of Wisconsin
Yong Liu PhD Assistant Professor in the Physiology department at Medical College of Wisconsin
Demin Wang PhD Assistant Professor in the Microbiology and Immunology department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Angiotensin II
Animals
Blood Pressure
Humans
Hypertension
Kidney
Male
MicroRNAs
Rats
Rats, Inbred Dahl
Sodium-Potassium-Exchanging ATPase
jenkins-FCD Prod-410 e9586552fe7f53c71f7923aa6e27aeabbd3c2473