Maguelonne Roux1,2, Claire Perret1,2, Eva Feigerlova3,4,5,6, Badreddine Mohand Oumoussa7, Pierre-Jean Saulnier3,4,5,6, Carole Proust1,2, David-Alexandre Trégouët1,2, Samy Hadjadj3,4,5,6. 1. Sorbonne Universités, UPMC Université Paris 06, INSERM UMR-S 1166, Paris, France. 2. ICAN Institute for Cardiometabolism and Nutrition, Paris, France. 3. CHU de Poitiers, Service d'Endocrinologie, Poitiers, France. 4. Université de Poitiers, UFR Médecine Pharmacie, Poitiers, France. 5. CHU de Poitiers, Centre d'Investigation Clinique, Poitiers, France. 6. INSERM, CIC 1402 & U1082, Poitiers, France. 7. Sorbonne Universités, UPMC Université Paris 06, Platform Post Genomic Pitié-Salpêtrière, Paris, France.
Abstract
Background: MicroRNAs (miRNAs) are small non-coding RNAs participating in post-transcriptional regulation of genes. Their key role in modulating the susceptibility to human diseases is now widely recognized, in particular in the context of cardiometabolic disorders. The aim of the present study was to identify miRNAs associated with diabetic nephropathy (DN) in patients with type 2 diabetes (T2D). Methods: A next-generation sequencing-based miRNA profiling was performed in a case-control study for DN in plasma samples of 23 T2D patients with DN (cases) and 23 T2D without (controls). The main associations were confirmed using quantitative reverse transcription-polymerase chain reaction and tested for replication in an independent case-control collection of 100 T2D patients, 50 with DN and 50 without. Results: From the 381 known mature miRNAs that were found highly expressed in the discovery samples, we observed and replicated an association between increased plasma levels of hsa-miR-152-3p and DN (P = 4.03 × 10-4 in the combined samples). Hsa-miR-152-3p plasma levels were further found to be positively correlated (P = 0.003) to plasma osmolarity, a surrogate marker for solute carrier net activity, whose regulation is controlled by several genes including SLC5A3, one of the predicted targets of hsa-miR-152-3p. Conclusions: We observed strong evidence for the association of hsa-miR-152-3p plasma levels and DN in patients with T2D, confirming an association previously observed in patients with type 1 diabetes.
Background: MicroRNAs (miRNAs) are small non-coding RNAs participating in post-transcriptional regulation of genes. Their key role in modulating the susceptibility to human diseases is now widely recognized, in particular in the context of cardiometabolic disorders. The aim of the present study was to identify miRNAs associated with diabetic nephropathy (DN) in patients with type 2 diabetes (T2D). Methods: A next-generation sequencing-based miRNA profiling was performed in a case-control study for DN in plasma samples of 23 T2D patients with DN (cases) and 23 T2D without (controls). The main associations were confirmed using quantitative reverse transcription-polymerase chain reaction and tested for replication in an independent case-control collection of 100 T2D patients, 50 with DN and 50 without. Results: From the 381 known mature miRNAs that were found highly expressed in the discovery samples, we observed and replicated an association between increased plasma levels of hsa-miR-152-3p and DN (P = 4.03 × 10-4 in the combined samples). Hsa-miR-152-3p plasma levels were further found to be positively correlated (P = 0.003) to plasma osmolarity, a surrogate marker for solute carrier net activity, whose regulation is controlled by several genes including SLC5A3, one of the predicted targets of hsa-miR-152-3p. Conclusions: We observed strong evidence for the association of hsa-miR-152-3p plasma levels and DN in patients with T2D, confirming an association previously observed in patients with type 1 diabetes.
Authors: Aml E Abdou; Haneya A A Anani; Hanan F Ibrahim; Eman Elshohat Ebrahem; Nora Seliem; Eman M I Youssef; Niveen M Ghoraba; Asmaa S Hassan; Marwa A A Ramadan; Eman Mahmoud; Shorouk Issa; Hend M Maghraby; Eman K Abdelrahman; Hala Ali Mohammed Hassan Journal: Tissue Barriers Date: 2021-10-23