Abstract 324: δ-Opioid Receptor Activation Modifies Hypoxic Expression of MicroRNAs in the Rat Kidney
Cardiovascular dysfunction often causes blood/oxygen insufficiency in the kidney that is very sensitive to changes in oxygen/blood delivery. Indeed, hypoxic/ischemic kidney stress is a frequent problem in clinical settings. There is, however, no promising strategy for prevention and treatment of such injury. Since recent studies suggest that microRNAs are differentially involved in hypoxic/ischemic events and delta-opioid receptor (DOR) activation increases antioxidant capacity and protects against hypoxic/ischemic injury, we asked if DOR activation regulates microRNA expression in the kidney under hypoxic condition. We isolated microRNAs from normoxic and hypoxic rat kidneys and used the paired microRNAs for microarray analysis. Thirty-one microRNAs were selected for quantitative PCR analysis based on the microarray data. Among them, 14 microRNAs were significantly altered in response to prolonged hypoxia for 1, 5 and 10 days, DOR activation with UFP-512 (1 mg/kg/day, ip, at days 0, 4 and 8) or a combination of both. Our novel data show that 1) DOR activation shifts miRNA expression profiles in normoxic conditions; 2) hypoxia differentially alters the miRNA expression profiles depending on hypoxic durations; and 3) DOR activation modifies hypoxia-induced changes in miRNA expression. For example, 10-day hypoxia reduced the level of miR-212 by >70% (p<0.001), while DOR activation could mimic such reduction even in normoxic kidney. In contrast, the same stress increased miR-29a by >100% (p<0.05), which could be attenuated by DOR activation. These results suggest that hypoxia comprehensively modifies the microRNA profile within the kidney, which can be mimicked or modified by DOR activation. Illumination of their targeted pathways, that regulate hypoxia sensitive transcription factors, antioxidant capacity, erythropoietin, Golgi-trafficking regulator, neurexophilin, ubiquitin-mediated degradation, intracellular trafficking, scaffolding, Wnt signaling, solute channels and ion homeostasis, may provide new insights into the potential therapeutics for hypoxic/ischemic injury of the kidney.
- © 2012 by American Heart Association, Inc.