Long noncoding RNAs may impact podocytes and proximal tubule function through modulating miRNAs expression in Early Diabetic Kidney Disease of Type 2 Diabetes Mellitus patients.
Aims: Long noncoding RNAs (lncRNAs) play key roles in the pathophysiology of DKD involving actions of microRNAs (miRNAs). The aims of the study were 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 in relation to a particular miRNAs profile. Methods: A total of 136 patients with type 2 DM and 25 healthy subjects were assessed in a cross-sectional study concerning urinary albumin: creatinine ratio (UACR), eGFR, biomarkers of podocyte damage (synaptopodin, podocalyxin) and of 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), urinary miRNA21, 124, 93, 29a. Results: Multivariable regression analysis showed that urinary lncMALAT1 correlated directly with urinary synaptopodin, podocalyxin, KIM-1, NAG, miRNA21, 124, UACR, and negatively with eGFR, miRNA93, 29a (p<0.0001; R2=0.727); urinary lncNEAT1 correlated directly with synaptopodin, KIM-1, NAG, miRNA21, 124, and negatively with eGFR, miRNA93, 29a (p<0.0001; R2=0.702); urinary lncMIAT correlated directly with miRNA93 and 29a, eGFR (p<0.0001; R2=0.671) and negatively with synaptopodin, KIM-1, NAG, UACR, miRNA21, 124 (p<0.0001; R2=0.654); urinary lncTUG1 correlated directly with eGFR, miRNA93, 29a, and negatively with synaptopodin, podocalyxin, NAG, miRNA21, 124 (p<0.0001; R2=0.748). Conclusions: In patients with type 2 DM lncRNAs exert either deleterious or protective functions within glomeruli and PT. LncRNAs may contribute to DKD through modulating miRNAs expression and activities. This observation holds true independently of albuminuria and DKD stage.
['Petrica|Ligia|L|', 'Hogea|Elena|E|', 'Gadalean|Florica|F|', 'Vlad|Adrian|A|', 'Vlad|Mihaela|M|', 'Dumitrascu|Victor|V|', 'Velciov|Silvia|S|', 'Gluhovschi|Cristina|C|', 'Bob|Flaviu|F|', 'Ursoniu|Sorin|S|', 'Jianu|Dragos Catalin|DC|', 'Matusz|Petru|P|', 'Pusztai|Agneta-Maria|AM|', 'Motoc|Andrei|A|', 'Cretu|Octavian M|OM|', 'Radu|Dana|D|', 'Milas|Oana|O|', 'Golea-Secara|Alina|A|', 'Simulescu|Anca|A|', 'Mogos-Stefan|Maria|M|', 'Patruica|Mihaela|M|', 'Balint|Lavinia|L|', 'Ienciu|Silvia|S|', 'Vlad|Daliborca|D|', 'Popescu|Roxana|R|']
D000328:Adult D000368:Aged D015415:Biomarkers D003430:Cross-Sectional Studies D003924:Diabetes Mellitus, Type 2 D003928:Diabetic Nephropathies D005260:Female D005786:Gene Expression Regulation D006801:Humans D007687:Kidney Tubules, Proximal D008297:Male D035683:MicroRNAs D008875:Middle Aged D050199:Podocytes D065840:Protective Factors D062085:RNA, Long Noncoding D012307:Risk Factors D055815:Young Adult
podocyte proximal tubule miRNA diabetes mellitus lncRNA