P1005LONG NONCODING RNAS MAY INTERVENE IN PODOCYTE INJURY AND PROXIMAL TUBULE DYSFUNCTION THROUGH MODULATING MIRNAS EXPRESSION IN EARLY DIABETIC KIDNEY DISEASE OF TYPE 2 DIABETES MELLITUS PATIENTS. (6th June 2020)

• Record Type: Journal Article
• Authors: Petrica, Ligia; GADALEAN, FLORICA; VLAD, ADRIAN; Vlad, Mihaela; DUMITRASCU, VICTOR; VELCIOV, SILVIA; Gluhovschi, Cristina Anca; Bob, Flaviu; URSONIU, SORIN; JIANU, CATALIN; MATUSZ, PETRU; Pusztai, Agneta; CRETU, OCTAVIAN; OANA, MILAS; GOLEA-SECARA, ALINA; SIMULESCU, ANCA; MOGOS-STEFAN, MARIA; PATRUICA, MIHAELA; POPESCU, ROXANA; Vlad, Daliborca
• Is Part Of: Nephrology dialysis transplantation. Volume 35(2020)Supplement 3
• Publication Date: 2020-06-06
• Subjects: Nephrology -- Periodicals; Hemodialysis -- Periodicals; Kidneys -- Transplantation -- Periodicals; Hemodialysis; Kidneys -- Transplantation; Nephrology; Periodicals; 616.61
• DOI: 10.1093/ndt/gfaa142.P1005
• Languages: English
• ISSNs: 0931-0509

Abstract

Abstract: Background and Aims: Interactions among multiple molecules and signalling pathways contribute to the pathogenesis and progression of diabetic kidney disease (DKD). Long noncoding RNAs (lncRNAs) play key roles in the pathophysiology of DKD involving actions of microRNAs (miRNAs). The aim of the study was to establish the involvement of selected lncRNAs in the epigenetic mechanisms of podocyte damage and tubular injury in DKD of type 2 diabetes mellitus (DM) patients. The molecular mechanisms of lncRNAs intervention were evaluated in relation to a particular miRNA profile. Method: A total of 136 patients with type 2 DM and 25 healthy subjects were enrolled in a cross-sectional case series study and assessed concerning urinary albumin: creatinine ratio (UACR), eGFR, biomarkers of podocyte damage (synaptopodin, podocalyxin) and proximal tubule (PT) dysfunction (Kidney injury molecule-1-KIM-1, N-acetyl-D-glucosaminidase-NAG), urinary lncRNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), nuclear-enriched abundant transcript 1 (NEAT1), myocardial infarction-associated transcript (MIAT), taurine-upregulated gene 1 (TUG1), and urinary miRNA21, 124, 93, 29a (quantified by a real-time PCR System). Results: Multivariable regression analysis yielded models in which urinary lncRNA MALAT1 correlated directly with urinary synaptopodin, podocalyxin, KIM-1, NAG, miRNA21, 124, UACR, and negatively with eGFR, miRNA93 and 29a (p<0.0001; R 2 =0.727); urinary lncRNA NEAT1 correlated directly with synaptopodin, KIM-1, NAG, miRNA21, 124, and negatively with eGFR, miRNA93, and 29a (p<0.0001; R 2 =0.702); urinary lncRNA MIAT correlated directly with miRNA93 and 29a, and eGFR (p<0.0001; R 2 =0.671) and negatively with synaptopodin, KIM-1, NAG, UACR, miRNA21, and 124 (p<0.0001; R 2 =0.654); urinary lncRNA TUG1 correlated directly with eGFR, miRNA93 and 29a, and negatively with synaptopodin, podocalyxin, NAG, miRNA21, and 124 (p<0.0001; R 2 =0.748). The results provided document upregulated lncRNA MALAT1 and NEAT1, as well as miRNA21 and 124. By contrast, lncRNA MIAT and TUG1, and miRNA93 and 29a were downregulated. Conclusion: In patients with type 2 DM lncRNAs exert distinct functions in different cell types, either deleterious or protective, at both glomerular and tubular level. LncRNAs may contribute to DKD through modulating miRNAs expression and activities. This observation holds true independently of albuminuria and DKD stage.