Abstract
Objectives
Mature microRNAs (miRNAs) are single-stranded RNAs approximately 22 nucleotides in length that act as posttranscriptional regulators by base-pairing with complementary sequences to mRNAs, leading to the silencing of mRNA. Circulating miRNAs may also serve as biomarkers for renal dysfunction including renal fibrosis which results in a progressive loss of renal function. We assessed circulating levels of miRNAs in the blood of dogs that were clinically diagnosed as having chronic kidney disease (CKD), post-mortem.
Methods
We used Qiagen's Canine mScript miRNA PCR array from blood samples that were collected at necropsy from dogs with CKD (n = 10; 2–17 yr) and control dogs (n = 10; 5–13.5 yr). End-of-life pathology reports indicated interstitial inflammation, fibrosis, and thickening of the Bowman's capsule.
Results
There was a significant decline in the levels of miRNAs cfa-let-7a, let-7c, let-7f, and let-7g in dogs with CKD when compared to controls (P < 0.05). Down-regulation of certain let-7 miRNAs (let-7a, let-7b) has been associated with experimental models of induction of renal fibrogenesis. There was also a > 2-fold reduction (ns) in levels of cfa-miR-93, cfa-miR-122, cfa-miR-200a, and cfa-miR-204, in CKD when compared to controls. These microRNAs have been demonstrated to have anti-fibrogenesis effect, and are also down-regulated in rodent models and in vitro mechanistic models of renal fibrosis leading to increased fibrosis. There was also a down-regulation of cfa-miR-16, which is consistent with its reported role in attenuating kidney injury independent of fibrosis. Taken together with the literature, down-regulation of these miRNAs may be indicative of a reduction in their role in attenuating renal fibrogenesis and injury. Importantly, the circulating miRNAs may serve as non-invasive biomarkers for renal fibrosis in CKD and also as nutritional targets for slowing the progression of fibrosis in kidney disease.
Conclusions
Our data show evidence of renal fibrosis markers that could have contributed to a progressive decline in kidney function. Nutritional therapy to slow the progression of kidney dysfunction may benefit from dietary ingredients including polyphenols that have been shown to upregulate miRNAs.
Funding Sources
Funded by Hills PNC, Inc.
Potential to Target Circulating miRNAs, Indicative of Renal Fibrosis, in Canines with Chronic Kidney Disease Through Dietary Intervention