Background Long noncoding RNA ANRIL has been found to be involved in the pathogenesis of diabetic kidney disease (DKD) and is expected to be a new target for prevention of DKD. However, the circulating expression and clinical significance of ANRIL in DKD patients is uncertain. This study aims to explore this issue. Methods The study consisted of 20 healthy controls, 22 T2DM patients (normalbuminuria) and 66 DKD patients (grouped as follows: microalbuminuria, n = 23; macroalbuminuria, n = 22 and renal dysfunction, n = 21). The expressions of ANRIL in peripheral whole blood of all participants were measured by RT-qPCR. Results The expression of ANRIL was significantly up-regulated in DKD patients (microalbuminuria, macroalbuminuria and renal dysfunction groups) than that in healthy control group. ANRIL was also over-expressed in macroalbuminuria and renal dysfunction groups in comparison with normalbuminuria group. ANRIL expression was positively correlated with Scr, BUN, CysC, urine β2-MG and urine α1-MG; while negatively correlated with eGFR in DKD patients. In addition, ANRIL was the risk factor for DKD with OR value of 1.681. The AUC of ANRIL in identifying DKD was 0.922, and the sensitivity and specificity of DKD diagnosis were 83.3% and 90.5%, respectively. Conclusion Our results indicated that highly expressed ANRIL in peripheral blood is associated with progression of DKD. Circulating ANRIL is an independent risk factor of DKD and has a highly predictive value in identifying DKD.

Objective. We aimed to investigate the role of ganoderic acid A (GAA) in glomerular mesangial cells (GMCs) under high glucose (HG). Methods. GMCs were pretreated with GAA and then cultured under HG condition for 24 h. Cell proliferation was measured by CCK-8 assay. The production of intracellular ROS was determined using DCFH-DA. The activities of SOD and CAT were measured using ELISA kits. The expressions of NOX2, NOX4, fibronectin (FN), collagen IV (col IV), p38, and p-p38 were detected by western blot. Results. GAA suppressed GMC proliferation in response to HG stimulation. GAA significantly attenuated HG-caused increase in ROS production and decreases in SOD and CAT activities in GMCs. In addition, the increased expressions of NOX2 and NOX4 and NOX activity in HG-induced GMCs were significantly decreased by GAA. Furthermore, GAA greatly inhibited the levels of FN and col IV in HG-stimulated GMCs. Mechanistic investigations showed that HG caused activation of p38 MAPK pathway, whereas the induction was mitigated by GAA. Notably, the specific agonist of p38 MAPK pathway (P79350) reversed the effects of GAA on GMCs. Conclusion. GAA protected GMCs from HG-induced oxidative stress and ECM production, which was mediated by the inhibition of the p38 MAPK pathway.

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