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Abstract
Kidney biopsy is considered the golden criterion for diagnosing the etiology of kidney disease but accompanied by non-negligible complications. We explored the possibility of using urinary microRNA (miRNA) as a non-invasive biomarker for hypertensive kidney injury. We assessed differential miRNA expressions in the kidneys and urine of hypertensive mice with kidney injury induced by deoxycorticosterone acetate (DOCA)-salt compared to the controls. DOCA-salt treatment significantly increased renal tubular lesions from day 2 and mRNA expression of fibrosis-related genes from day 4 compared to the controls, respectively. Urinary albumin and N-acetyl-beta-D-glucosaminidase was significantly increased on day 8 compared to the controls. Array results showed that 20 out of 585 miRNAs were highly expressed in the kidneys and significantly increased on day 8 compared to the controls, including miR-21, miR-146b, miR-155 and miR-132, which were confirmed by real-time polymerase chain reaction and were significantly higher from day 4. The miR-21/creatinine in the urine from day 4 was significantly higher than that of the controls and was detected earlier than urinary albumin. In conclusion, we have identified urinary miR-21 that correlates with histopathological lesions and functional markers of kidney damage to facilitate a potential noninvasive detection for hypertensive kidney injury.
Highlights
Hypertension is a major risk factor for stroke, myocardial infarction, and kidney failure[1]
Expression changes of miRNAs have been reported in renal disease, including renal tumors[12], diabetic nephropathy[13,14], immunoglobulin-A nephropathy[15], and acute rejection after renal transplantation[16,17]
We assessed differential expression levels of miRNAs in the kidneys and urine of deoxycorticosterone acetate (DOCA)-salt induced hypertensive mice compared to the controls to determine the worthy miRNAs in the early detection of hypertensive kidney injury and fibrosis
Summary
Hypertension is a major risk factor for stroke, myocardial infarction, and kidney failure[1]. Noninvasive markers of kidney disease etiology could promote clinical medicine by replacing a currently invasive procedure and improve diagnostic accuracy in patients who do not undergo a biopsy. Circulating miRNAs have been shown to be useful as diagnostic biomarkers in kidney disease and in various cancer, liver disease, and myocardial injuries[10,18,19]. Some qualities, such as abundant expression, tissue specificity, stability, and evolutionary conservation make extracellular miRNAs attractive as noninvasive biomarkers that reflect disease states[20]. We assessed differential expression levels of miRNAs in the kidneys and urine of deoxycorticosterone acetate (DOCA)-salt induced hypertensive mice compared to the controls to determine the worthy miRNAs in the early detection of hypertensive kidney injury and fibrosis
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