Renin expression downregulated by microRNAs in hypertension
MedWire News: MicroRNAs are able to regulate renin expression, an international team of researchers have discovered.
The molecular etiology of hypertension is still relatively unknown, with studies of blood pressure genes identifying only a small number of gene variants that have small effect sizes. However, the concept is that hypertension is caused by a primary defect in the kidney.
Noting that microRNAs play an important role in several physiologic and pathophysiologic processes, Brian Morris, from the University of Sydney, in New South Wales, Australia, and colleagues studied the expression of messenger RNAs (mRNAs) and microRNAs in 15 untreated hypertensive male patients and seven normotensive males, all of whom were of white European ancestry.
The results, published in the journal Hypertension, revealed that, in the medulla, 14 genes and 11 microRNAs were differentially expressed between the two groups on microarray technology. Realtime quantitative polymerase chain reaction analysis was then used to confirm the differential expression of the mRNAs NR4A1, NR4A2, NR4A3, PER1, and SIK1, and the microRNAs hsa-miR-638 and hsa-let-7c.
Forty-six mRNAs and 13 microRNAs were differentially expressed between hypertensive and normotensive individuals in the renal cortex, of which the mRNAs AIFM1, AMBP, APOE, CD36, EFNB1, NDUFAF1, PRDX5, REN, RENBP, SLC13A1, STX4, and TNNT2, and the micoRNAs hsa-miR-21, hsa-miR-126, hsa-miR-181a, hsa-miR-196a, hsa-miR-451, hsa-miR-638, and hsa-miR-663 were confirmed.
HEK293 human kidney cells were then used to examine functional correlates of altered microRNA expression. In the medulla, hsa-let-7c was confirmed as binding to the 3' untranslated region of NR4A2 mRNA. In the renal cortex, hsa-miR-663 was found to be capable of regulating REN and APOE mRNA levels, while hsa-miR-181a regulated REN and AIFM1 mRNA.
The team writes: "It has for many decades been argued that renin is involved in the etiology of essential hypertension. Molecular genetics has, however, failed to implicate REN polymorphisms. Thus, our finding of REN overexpression, coupled with the discovery of downregulation of 2 microRNAs that bind to and affect REN mRNA levels, is the first real evidence to implicate renin."
Co-author Maciej Tomaszewski, from the University of Leicester, in the UK, commented in a press statement: "I am very excited about this publication. Renin is one of the most important contributors to blood pressure regulation. The novel insights into its expression within the human kidney from this study open up new avenues for the development of new antihypertensive medications."
By Liam Davenport