Circulating long non-coding RNA expression profiles in diabetes and diabetic nephropathy patients

LYU Xiao-meng; FAN Qiu-ling; WANG Xu; XU Li; LU Xin-xing; CHEN Tong; WANG Li-ning

doi:10.19538/j.nk2017030110

Abstract：Objective To elucidate the epigenetics mechanism and to explore the new biomarkers of diabetes and diabetic nephropathy by analyzing the circulating lncRNA and mRNA expression profiles of normal controls and patients with diabetes mellitus,diabetic nephropathy.Methods Serum samples from 21 diabetic nephropathy patients proven by renal biopsy as nodular diabetic glomerulosderosis,9 diabetic patients without microalbuminuria (DM) and 19 healthy controls (N) were collected.Serum LncRNA and mRNA expression profiles were analyzed with Arraystar Human LncRNA/mRNA V3.0 expression spectrum biochips.Agilent Feature Extraction software was used to extract the information contained in the microarray images.GeneSpring GX software was used to further screen the original expression information of LncRNA and mRNA.Results The urinary microalbumin/creatinine ratio and serum creatinine of diabetic nephropathy patients were higher and the estimated glomeruar filtration rate(eGFR)was lower than those of diabetic patients and healthy controls (P＜0.05).Totally 245 lncRNAs were upregulated and 680 lncRNAs were downregulated in serum of diabetic patients compared with those of healthy controls.Totally 45 lncRNAs were upregulated and 813 lncRNAs were downregulated in serum of diabetic nephropathy patients compared with those of diabetic patients.Along with the progression of diabetes and diabetic nephropathy,lncRNA-ARAP1-AS2 was gradually increased (2.82 times in DM/N and 2.47 times in DN/DM),hicRNA-ARAP1-AS1 was gradually reduced (2.24 times in DM/N,4.79 times in DN/DM),and their target gene AT1 receptor-associated protein 1 (ARAP 1)mRNA was gradually increased (2.25 times in DM/N and 2.45 times in DN/DM).Condusions The down-regulation of lncRNA-ARAP1-AS1 and upregulation of lncRNA-ARAP1-AS2 upregulated ARAP1 mRNA expression and may involve in the pathogenesis of diabetes and DN via functioning on mRNA-ARAP1.By increasing the sensitivity of AT1 receptor to angiotensin Ⅱ,circulatting lncRNA-ARAP1-AS1,lncRNA-ARAP1-AS2 and ARAP1 may be new biomarkers for diabetes and diabetic nephropathy.