Abstract
Background: The kidney has long been considered to have an important role in hypertension etiology. Methods: Using transcriptomics we identified 60 mRNAs and 24 miRNAs differentially expressed in renal cortex and medulla between European hypertensive and normotensive subjects. Confirmation was by real-time quantitative PCR. Functional experiments were conducted. Bioinformatic analyses, involving gene ontology (GO) analysis and gene set test (GST), were used to identify disturbances in intracellular pathways. Results: The sodium transport regulator SIK1, APOE, NR4A1–3, and renin were overexpressed in hypertension. CD36 was under-expressed, as in the SHR. Bioinformatic predictions of miRNA target sites in several genes of particular interest, including renin, were confirmed by co-transfection experiments involving microRNA mimics in a human kidney cell line. By GST for cortex data, terms identified included renin-angiotensin system, electron transport chain, mitochondrial respiratory chain complex I, regulation of transcription. By GO terms included sodium ion transport, nitric oxide mediated signal transduction, circulatory system process, response to reactive oxygen species, signalling, urea cycle and apoptosis. In the medulla, GST revealed sodium ion transport, sodium ion binding, symporter activity, oxidation reduction, mitochondrial inner membrane, ATP binding, apical plasma membrane, transmembrane transport, transporter activity and regulation of transcription. GO analysis identified calcium-mediated signalling, regulation of transcription, developmental processes, negative regulation of apoptosis, regulation of catecholamine metabolic process, dephosphorylation, RNA metabolic process, inactivation of MAP kinase activity, cytokine receptor binding, spliceosome and endocytosis. Conclusions: These new findings illuminate mechanistic disturbances and should assist in understanding hypertension pathophysiology. Novel treatment strategies could ensue.
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