Serum, Urine, and Kidney MicroRNA and Gene Expression Characterization in Dogs with Chronic Kidney Diseases
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Chronic kidney disease (CKD) is a significant cause of death in dogs. However, the gene and microRNA (miRNA) expression profile that affects progression in CKD has only been partially characterized. Dogs with X-linked hereditary nephropathy (XLHN) have a glomerular basement membrane defect that leads to progressive juvenile-onset renal failure, and their disease is analogous to Alport syndrome in humans. Therefore, dogs with XLHN not only serve as a good model of canine CKD but also an animal model for Alport syndrome in humans. In the report, kidney tissue mRNA and small RNA sequencing were used to aid in the characterization of CKD progression in colony dogs with XLHN. Further, biofluid miRNA expression in serum and urine was characterized to serve as potential biomarkers in canine patients with natural-occurring glomerular diseases. Differentially expressed genes (DEGs) and differentially expressed miRNAs (DE miRs) were identified via mRNA and small RNA sequencing in serial kidney biopsies obtained from dogs with XLHN. The DEGs and the top-ranked miRNA target genes derived from DE miRs were used to identify enriched biological processes, overrepresented pathways, and upstream regulators that contribute to kidney disease progression. Differentially expressed genes and DE miRs identified over 3 clinical time points revealed upregulation of inflammatory pathways, and TGF-b1 was identified as the primary upstream regulator. These results provide new insights into the underlying molecular mechanisms of disease progression in XLHN, and the identified DEGs and DE miRs can be potential biomarkers and therapeutic targets translatable to all CKDs. Biofluid miRNA detection was performed in carrier female dogs with XLHN. This preliminary study helped optimize RNA isolation and library preparation methods for canine serum and urine. A biofluid miRNA biomarker study was then performed in dogs with 3 types of glomerular diseases diagnosed histopathologically: focal segmental glomerulosclerosis, immune complex glomerulonephritis, and amyloidosis. Compared with healthy control dogs, DE miRs were identified in the serum and urine from dogs with mild or advanced tubulointerstitial fibrosis in all 3 diseases. Several miRs showed promise in their ability to distinguish among these 3 glomerular diseases. These results will provide non-invasive options for diagnosing canine glomerular diseases.
chronic kidney disease
X-linked hereditary nephropathy
Chu, Pei-Hua (2018). Serum, Urine, and Kidney MicroRNA and Gene Expression Characterization in Dogs with Chronic Kidney Diseases. Doctoral dissertation, Texas A&M University. Available electronically from