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Abstract: TH-PO891

Small RNA Sequencing Identifies Circulating sncRNAs That Are Differentially Expressed in Type 1 Diabetic Patients at Risk of Progressive Renal Decline

Session Information

Category: Diabetic Kidney Disease

  • 601 Diabetic Kidney Disease: Basic

Authors

  • Pezzolesi, Marcus G., University of Utah, Salt Lake City, Utah, United States
  • Satake, Eiichiro, Joslin Diabetes Center, Boston, Massachusetts, United States
  • Kato, Mitsuo, City of Hope , Duarte, California, United States
  • Lazaro guevara, Jose M., University of Utah, Salt Lake City, Utah, United States
  • Bitzer, Markus, University of Michigan, Ann Arbor, Michigan, United States
  • Natarajan, Rama, Beckman Research Institute of City of Hope, Duarte, California, United States
  • Krolewski, Andrzej S., Joslin Diabetes Center, Boston, Massachusetts, United States
Background

Progressive renal decline is the fundamental disease process that underlies the development of end-stage renal disease (ESRD) in Type 1 diabetes (T1D). Work by our group and others has demonstrated that microRNA (miRNA) expression profiles are altered in T1D patients with diabetic nephropathy. In the present study, we used small RNA sequencing (sRNA-Seq) to identify circulating small non-coding RNAs (sncRNAs), non-coding regulatory RNAs typically 18-200 nucleotides in length, that are associated with progressive renal decline in T1D patients with normal renal function (eGFR>60 ml/min per 1.73m2) from the Joslin Kidney Study (JKS).

Methods

sRNA-Seq was used to determine circulating sncRNA expression profiles in baseline plasma specimens obtained from two sub-groups of patients who were followed for 5-10 years from entry to the JKS: 76 rapid progressors, who experienced significant loss of renal function over the course of their follow-up (eGFR slope=-12.61 ml/min/1.73m2/year), and 70 non-progressors, who experienced minimal decline in eGFR during their follow-up (eGFR slope=-1.43 ml/min/1.73m2/year).

Results

Differential expression analysis identified more than 50 sncRNAs, including miRNAs, small nucleolar RNAs (snoRNAs), and small nuclear RNAs (snRNAs), that were significantly differentially expressed among rapid progressors and non-progressors, including miR-3168 (P = 8.7x10-7), SNORD36C (P = 1.1x10-6), and SNORD30 (P = 3.7x10-6). Interestingly, we also found miR-3168 to be differentially expressed in an independent cohort of non-progressors and rapid progressors with impaired renal function from the JKS (P-value = 0.0006).

Conclusion

These data suggest that sncRNAs, including miR-3168, SNORD36C, and SNORD30, may be able to distinguish diabetic individuals who are at the greatest risk of losing renal function from those who are protected against these complications. The differentially expressed sncRNAs identified in this study represent novel therapeutic targets that may prove useful in inhibiting renal function decline in T1D.

Funding

  • NIDDK Support