Hypertension is a major risk factor for chronic kidney disease (CKD) and renal inflammation is an integral part in this pathology. Hydrogen sulfide (H2S) has been shown to mitigate renal damage through reduction in blood pressure and reactive oxygen species; however, the exact mechanisms are not clear. While several studies have underlined the role of epigenetics in renal inflammation and dysfunction, the mechanisms through which epigenetic regulators play role in hypertension are not well defined. In this study, we sought to identify if microRNAs are dysregulated in response to angiotensin-II (Ang-II) induced hypertension in the kidney and whether H2S donor, GYY 4137, could reverse the microRNA alteration and kidney function. Wild-type (C57BL/6J) mice were treated without or with Ang-II and GYY4137 for 4 weeks. Blood pressure, renal blood flow and resistive index (RI) were measured. MicroRNA microarrays were conducted and subsequent target prediction revealed genes associated with pro-inflammatory response. Ang-II treatment significantly increased blood pressure, decreased blood flow in the renal cortex, and increased in RI and reduced renal function. These effects were ameliorated in mice treated with GYY4137. Microarray analysis revealed downregulation of miR-129 in Ang-II treated mice and upregulation following GYY4137 treatment. Quantitation of proteins involved in inflammatory response and DNA methylation revealed upregulation of IL-17A and DNMT3a while H2S production enzymes and anti-inflammatory IL-10 were reduced. Taken together, our data suggests that downregulation of miR-129 plays a significant role in Ang-II induced renal inflammation and functional outcomes, and GYY4137 improves renal function by reversing miR-129 expression.
- hydrogen sulfide
- Copyright © 2016, American Journal of Physiology-Heart and Circulatory Physiology