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Detection of MicroRNA Expression in the Kidneys of Immunoglobulin A Nephropathic Mice
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MiR-192-5p in the Kidney Protects Against the Development of Hypertension

Maria Angeles Baker1, Feng Wang1,2, Yong Liu1

  • 1From the Department of Physiology, Center of Systems Molecular Medicine, Medical College of Wisconsin, Milwaukee (M.A.B., F.W., Y.L., A.J.K., A.M.G., K.U., H.X., D.W., Y.K., M.L.).

Hypertension (Dallas, Tex. : 1979)
|January 1, 2019
PubMed

Insights

MicroRNA miR-192-5p, abundant in the kidney, protects against hypertension by targeting ATP1B1. Lower miR-192-5p levels correlate with hypertension, and its inhibition exacerbates high blood pressure in animal models.

Area of Science:

  • Nephrology
  • Molecular Biology
  • Cardiovascular Research

Background:

  • MicroRNAs (miRNAs) play crucial roles in regulating gene expression.
  • miR-192-5p is highly expressed in the kidney and targets ATP1B1, a key component of Na+/K+-ATPase.
  • Na+/K+-ATPase is essential for renal tubular reabsorption and blood pressure regulation.

Purpose of the Study:

  • To investigate the role of kidney miR-192-5p in the development of hypertension.
  • To determine if reduced miR-192-5p levels contribute to hypertension.
  • To elucidate the mechanism by which miR-192-5p influences blood pressure.

Main Methods:

  • Analysis of miR-192-5p levels in kidney biopsy specimens from hypertensive patients and controls.
  • Comparison of renal miR-192-5p abundance in Dahl salt-sensitive rats and a less salt-sensitive congenic strain.
  • Experimental manipulation of miR-192-5p levels in rats and mice using anti-miR therapies and gene knockout models.
  • Assessment of blood pressure, ATP1B1 protein levels, and Na+/K+-ATPase activity.

Main Results:

  • miR-192-5p levels were significantly lower in kidneys of patients with hypertension and in Dahl salt-sensitive rats compared to controls.
  • Inhibition of miR-192-5p in rats and mice led to a significant exacerbation of hypertension, particularly on a high-salt diet.
  • miR-192-5p knockout mice exhibited elevated blood pressure when treated with Angiotensin II.
  • ATP1B1 protein levels were higher in hypertensive rats, and Na+/K+-ATPase activity increased upon miR-192-5p inhibition.
  • Knockdown of ATP1B1 attenuated hypertension in rats with concurrent miR-192-5p knockdown.

Conclusions:

  • Kidney miR-192-5p plays a protective role against the development of hypertension.
  • This protective effect is, at least partly, mediated through the targeting of Atp1b1 mRNA, influencing Na+/K+-ATPase function.
  • Reduced miR-192-5p may be a contributing factor to hypertension pathogenesis.
Keywords:
diethypertensionkidneymicroRNArats

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