Abstract
Hypertension is a major risk factor for chronic kidney disease and renal inflammation is an integral part in this pathology. In recent years, hydrogen sulfide (H2S) has emerged as an important regulator of blood pressure. Studies in spontaneously hypertensive rats have shown that endogenous hydrogen sulfide (H2S) production is impaired due to decreased CBS/CSE expression, and exogenous H2S supplementation decreased blood pressure and vascular remodeling. MicroRNAs are short, single‐stranded RNA genes that regulate post‐transcriptional gene expression by targeting messenger RNAs (mRNAs), and are associated with a broad spectrum of physiological processes. While there are several studies aimed at investigating the role of non‐coding RNA in hypertension, the roles and implications of these RNAs are not well defined. In this study, we sought to identify microRNAs that are dysregulated in response to angiotensin‐induced hypertension in the kidney and whether hydrogen sulfide donor, GYY 4137, could reverse the microRNA alteration. Wild‐type mice were treated without or with Ang‐II (1000ng/Kg/Min) and without or with GYY4137 for 4 weeks. Blood pressure, renal blood flow, renal resistive index (RI) measurements were performed. microRNA microarrays were conducted and subsequent target prediction revealed genes associated with proinflammatory response. Ang‐II treated mice showed a significant increase in blood pressure accompanied by a decrease in blood flow in the renal cortex and an increase in the resistive index. These effects were attenuated in mice treated with GYY4137. Microarrays of the kidneys revealed downregulation of miR‐129 and miR‐299b in Ang‐II treated mice and upregulation following GYY4137 treatment. In contrast, miR‐369 was upregulated in Ang‐II treatment and suppressed in Ang‐II+GYY4137 mice. Quantitation of genes involved in proinflammatory response revealed upregulation of Tnfα, Il1β, Mcp1 and Mip2 mRNA. Our data suggests that downregulation of miR‐129 and ‐299b plays a significant role in Ang‐II induced renal inflammation, and GYY4137 reduces inflammation and is associated with reversal of miR expression.Support or Funding InformationNIH: HL104103, AHA: 15SDG25840013
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