MiR-192-5p in the Kidney Protects Against the Development of Hypertension. Hypertension 2019 Feb;73(2):399-406
Date
01/01/2019Pubmed ID
30595117Pubmed Central ID
PMC6339564DOI
10.1161/HYPERTENSIONAHA.118.11875Scopus ID
2-s2.0-85059796489 (requires institutional sign-in at Scopus site) 42 CitationsAbstract
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.13BN26 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.13BN26 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.13BN26 rats. Na+/K+-ATPase activity increased in the renal cortex of SS.13BN26 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.13BN26 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 MAuthors
Aron Geurts PhD Professor in the Physiology department at Medical College of WisconsinAlison J. Kriegel PhD Associate Professor in the Physiology department at Medical College of Wisconsin
Demin Wang PhD Professor in the Microbiology and Immunology department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
Angiotensin IIAnimals
Blood Pressure
Humans
Hypertension
Kidney
Male
MicroRNAs
Rats
Rats, Inbred Dahl
Sodium-Potassium-Exchanging ATPase