Abstract: SA-PO314
Mature MicroRNA (miRNA)-1287-5p and miRNA-197-5p Are Upregulated in Diabetic Kidney Disease
Session Information
- Diabetic Kidney Disease: Clinical Pathology, Diagnostic and Treatment Advances
October 26, 2024 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Diabetic Kidney Disease
- 702 Diabetic Kidney Disease: Clinical
Authors
- Wilson, Jonathan Matthew, Eli Lilly and Company, Indianapolis, Indiana, United States
- Satake, Eiichiro, Harvard University, Cambridge, Massachusetts, United States
- Najafian, Behzad, University of Washington, Seattle, Washington, United States
- Duffin, Kevin L., Eli Lilly and Company, Indianapolis, Indiana, United States
- Krolewski, Andrzej S., Harvard University, Cambridge, Massachusetts, United States
Background
Our previous study examined tissue expression levels of circulating risk miRNAs associated with end-stage kidney disease (ESKD) in diabetes (Satake et al, JASN 2021). The current study aims to extend these finding with larger cohorts and additional analyses of specific ESKD risk miRNAs to understand expression levels and cellular localization in diabetic kidney.
Methods
Localization and levels of mature miRNAs were examined in kidney specimens using a miRNAscope in situ hybridization (ISH) assay. Optimized in silico–designed miRNAscope probes for miR-1287-5p and miR-197-5p were utilized for analyses of kidney tissue expression. Probes were hybridized to formalin-fixed paraffin embedded sections of kidney biopsy tissue obtained from 8 healthy donors (controls), and persons with mild (N=6) or advanced (N=8) biopsy proven diabetic kidney disease (DKD).
Results
miR-1287-5p and miR-197-5p were detected more abundantly in DKD tissues than in controls. miRNA-197-5p was detected at a higher level than miRNA-1287-5p in DKD sections. In DKD, miR-1287-5p and miR-197-5p were detected in tubular epithelia (with more abundance in distal tubules) and glomeruli. Both miRNAs were detected in focal areas of infiltrating inflammatory cells. Both miRNAs were detected in the cytoplasm as well as the nuclei.
Conclusion
Our studies confirm that ESKD risk miRNAs (miRNA-1287-5p and miRNA-197-5p) have higher kidney tissue levels in DKD than normal, especially in tubular epithelial cells. miRNA-1287-5p was validated across multiple donor tissues to be present in DKD vs normal, while novel data show miRNA-197-5p was also present at higher levels in DKD tissue sections. Kidney may be a source of circulating ESKD miRNAs but cellular uptake of circulating miRNA into the kidney may also contribute to higher observed levels. Further studies of tissue expression patterns of ESKD miRNAs will help to advance our understanding of the pathology of DKD and the role of miRNA in disease signaling.
Funding
- Commercial Support – Lilly