Abstract: SA-PO168
The Blood Transcriptome Is Reflective of Renal Tissue Injury in Endotoxin-Associated Acute Kidney Failure
Session Information
- AKI: Mechanisms - III
November 04, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Acute Kidney Injury
- 103 AKI: Mechanisms
Authors
- Janosevic, Danielle, Indiana University School of Medicine, Indianapolis, Indiana, United States
- Martinez Lopez, Maria Fernanda, Universidad Iberoamericana, Santo Domingo, Dominican Republic
- De Luca, Thomas, Indiana University School of Medicine, Indianapolis, Indiana, United States
Background
MicroRNA (miR) regulate the translation of RNA involved in renal injury and recovery processes in endotoxin-associated acute kidney injury (sAKI). We previously identified the renal tissue response in sAKI as a series of temporally unique stages consisting of inflammation progressing to translation shutdown and organ failure. We hypothesize the blood miR and RNA (transcriptome) exhibits a response reflective of underlying renal tissue sAKI stage.
Methods
Kidney bulk RNAseq and miRNAseq were performed in an established murine model of sAKI at 0 (baseline) and 1,16 hr (injury) after endotoxin tail vein injection (LPS, n= 5 per timepoint). Total RNA (consisting of RNA and miRNA) extracted from bulk kidney tissue and whole blood (blood), DNAse treated, and globin depletion (blood only) performed. For each miR and RNA, libraries prepared and sequenced (miR: 10-15 million read depth/sample, RNA: 25-30 million read depth/sample) aligned to mm10 transcriptome (STAR). Counts were TMM normalized, log-transformed (counts-per-million, EdgeR), generating expression data. Pearson correlation between blood and kidney performed and common genes with r>0.8 and FDR <0.05 considered significantly correlated and pathway analysis performed (Pathfindr).
Results
Transcriptome analyses performed in the blood and the kidney revealed positively correlated miR (n=133 r > 0.8) and RNA (n= 388, r >0.99) shared between the blood and kidney at each timepoint. Pathway analysis revealed significant upregulation (p <0.05) of inflammatory, extracellular matrix/migratory pathways at 1 hr after LPS (NFKB pathway, cell-matrix adhesion, endothelial cell migration). At 16 hr after LPS there were shared alterations in transcription processing, miR regulation, viral responses, and catabolic processes. Analysis of the transcriptome shared between the blood and the kidney revealed parallel activation of RNA involved in the innate immune response and metabolic processes, regulated by miR (miR-144/Cxcl10, miR-298/Cd14, miR-345/Saa2).
Conclusion
Our data suggest that miR regulate RNA in several important sAKI-related pathways. These data demonstrate that the blood transcriptome may be reflective of underlying sAKI tissue stage indicating the utility of these transcriptomic biomarkers.
Funding
- Private Foundation Support