Abstract: FR-PO609

miRNA-27b and miRNA-1228 Urinary Levels Discriminate Specific Classes of Histological Damage in Diabetic Patients

Session Information

Category: Diabetes

  • 501 Diabetes Mellitus and Obesity: Basic - Experimental

Authors

  • Pontrelli, Paola, University of Bari-Dept. of Emergency and Organ Transplantation, Bari, Italy
  • Laviola, Luigi, University of Bari Aldo Moro , Bari, Italy
  • Simone, Simona, None, BARI, Italy
  • Rossini, M., University of Bari, Department of Emergency and Organ Transplantation, Nephrology Unit, Bari, Italy
  • Federici, Massimo, University of Rome Tor Vergata, Rome, Italy
  • Gesualdo, Loreto, University of Bari, Bari, Italy
  • Conserva, Francesca, University of Bari, Bari, Italy
  • Barozzino, Mariagrazia, University of Bari, Bari, Italy
  • Pesce, Francesco, University of Bari, Bari, Italy
  • Menghini, Rossella, University of Rome Tor Vergata, Rome, Italy
  • Oranger, Annarita, University of Bari, Bari, Italy
  • Di Franco, Antonella, University of Bari, Bari, Italy
  • Papale, Massimo, University of Bari, Bari, Italy
  • Giorgino, Francesco, University of Bari, Bari, Italy
Background

Diabetic nephropathy (DN) is the leading cause of end stage renal disease. Aim of our study was to identify novel urinary biomarkers which correlate with the histological damage. We focused on those miRNAs that modulate lysin63 ubiquitination, responsible of tubular damage in diabetic patients (PMID: 27881486).

Methods

Urinary samples were collected from 16 patients with type-2 diabetes (T2D) and DN, 7 with T2D and other nephrities (T2D-GN), including membranous nephropathy (MN) and Focal and Segmental Glomerulosclerosis (FSGS), 32 with other nephrities without T2D (GN), all with a biopsy proven diagnosis, 7 with T2D and normal renal function, 9 healthy subjects (HS). miRNAs expression was evaluated by qPCR in urines and in situ hybridization on tissues. Data were validated in a mouse model of DN (DBA2J mice treated with streptozotocin-STZ).

Results

miRNA-27b was down-regulated in urines of DN patients when compared to HS (p=0.03), to T2D (p=0.04) to T2D-GN (p=0.04), and to GN (p=0.05), such as miRNA-1228 (p=0.01 vs HS, p=0.01 vs T2D, p=0.04 vs T2D-GN, p=0.05 vs GN). Tissue expression of both miRNAs was also reduced at tubular level in DN vs T2D-GN (p<0.05) and was directly correlated with tubular-interstitial fibrosis (p<0.05). ROC curve from a predictive model (based on logistic regression) combining both miRNAs relative expression, was able to predict DN in the comparison with HS (AUC=0.93; p=5.9E-19), with T2D-GN (AUC=0.81; p=0.001), with T2D (AUC 0.90; p=2.7E-10) and with GN (AUC=0.69; p=0.002). miRNA-27b (conserved among species) was also down-regulated in urines of DBA2J/STZ mice vs DBA2J untreated controls (FC: -3.79; p<0.05) and was correlated with lysin63 protein accumulation and tubular-interstitial fibrosis (p<0.05).

Conclusion

miRNA-27b and -1228 expression correlate with increased fibrosis and discriminate DN patients vs other histological lesion in diabetic and non- diabetic patients.

Funding

  • Government Support - Non-U.S.