COMBINED EXOSOMAL AND PLASMA NON-CODING RNA SIGNATURE ASSOCIATED WITH URINARY ALBUMIN EXCRETION IN HYPERTENSION

Abstract

Objective: Non-coding RNA (ncRNA), released into circulation or packaged into exosomes, play important roles in many biological processes in the kidney. The purpose of the present study is to identify a common ncRNA signature associated with early renal damage and its related molecular pathways by constructing a RNA-based transcriptional network. Design and method: This is an observational case-control study which included 43 hypertensives, twenty-one patients with essential hypertension and twenty-two without persistent elevated urinary albuminuria (UAE) (higher or equal to 30 mg/g urinary creatinine). Three individual libraries (plasma and urinary exosomes and total plasma) were prepared from each hypertensive patient for ncRNA sequencing analysis. Next, a RNA-based transcriptional regulatory network was constructed. Results: The three RNA biotypes with the greatest number of differentially expressed transcripts were long-ncRNA (lncRNA), microRNA (miRNA) and piwi-interacting RNA (piRNA). We identified a common 24 ncRNA molecular signature related to hypertension-associated albuminuria, of which lncRNA was the most representative. In addition, the transcriptional regulatory network analysis showed five lncRNA (LINC02614, BAALC-AS1, FAM230B, LOC100505824 and LINC01484), and the miR-301a-3p to play a significant role in network organization and to target critical pathways regulating filtration barrier integrity, tubule reabsorption and systemic endothelial dysfunction. Conclusions: Our study found a combined ncRNA signature associated with albuminuria, independently of biofluid origin (urine or plasma, circulating or in exosomes) that identifies a handful of potential targets involved in filtration barrier, tubule reabsorption and endothelial function that may be utilized to treating hypertension-associated albuminuria and cardiovascular damage progression.