Urinary exosome-derived microRNAs reflecting the changes of renal function and histopathology in dogs

Area of Science:

• Veterinary Medicine
• Molecular Biology
• Biomarker Discovery

Background:

• MicroRNAs regulate gene expression post-transcriptionally.
• Urinary exosome (UExo)-derived microRNAs are potential non-invasive biomarkers.
• Canine kidney disease (KD) diagnosis and monitoring require improved methods.

Purpose of the Study:

• To screen for UExo-derived microRNAs that reflect kidney disease status in dogs.
• To identify specific microRNAs that correlate with renal dysfunction and histopathology.
• To evaluate the potential of UExo microRNAs as diagnostic and prognostic markers for canine KD.

Main Methods:

• Dogs were categorized into healthy control (HC) and KD groups based on renal function.
• Urinary exosomes were isolated and characterized using immunoblot detection of exosome markers (TSG101, CD9).
• Next-generation sequencing was employed to profile UExo-derived microRNAs, followed by quantitative analysis of candidate microRNAs (miR-26a, miR-146a, miR-486, miR-21a, miR-10a/b).

Main Results:

• UExo-derived miR-26a and miR-10a/b were significantly decreased in KD dogs, with miR-26a levels negatively correlating with renal function.
• UExo-derived miR-21a levels increased with renal dysfunction, particularly when normalized to specific internal controls.
• Kidney tissue analysis revealed decreased miR-26a and miR-10a/b in glomeruli and miR-10b in tubulointerstitium, correlating with disease severity; increased miR-21a in tubulointerstitium also correlated with histopathology.

Conclusions:

• Specific UExo-derived microRNAs, notably miR-26a and miR-10a/b, reflect changes in renal function and histopathology in dogs with KD.
• These microRNAs hold potential as non-invasive biomarkers for diagnosing and monitoring canine kidney disease.
• Further validation is warranted to establish their clinical utility in veterinary practice.