Abnormal Expression of miR-21 in Kidney Tissue of Dogs With X-Linked Hereditary Nephropathy: A Canine Model of Chronic Kidney Disease
| Autor: | Sabrina D. Clark, Shiguang Liu, Rachel E. Cianciolo, Wenping Song, George E. Lees, Mary B. Nabity |
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| Rok vydání: | 2018 |
| Předmět: |
medicine.medical_specialty
Pathology 040301 veterinary sciences Renal function Nephritis Hereditary 0403 veterinary science 03 medical and health sciences chemistry.chemical_compound Dogs Fibrosis Medicine Animals Dog Diseases Alport syndrome Renal Insufficiency Chronic ACADM 030304 developmental biology 0303 health sciences Creatinine Kidney General Veterinary business.industry Genetic Diseases X-Linked 04 agricultural and veterinary sciences medicine.disease MicroRNAs medicine.anatomical_structure chemistry Gene Expression Regulation Histopathology business Kidney disease |
| Zdroj: | Veterinary pathology. 56(1) |
| ISSN: | 1544-2217 |
| Popis: | MicroRNAs (miRNAs) are a group of small noncoding RNAs that act as regulators of posttranslational gene/protein expression and are known to play a key role in physiological and pathological processes. The objective of our study was to compare expression of miR-21 in renal tissue from dogs affected with chronic kidney disease (CKD) caused by X-linked hereditary nephropathy (XLHN), a disease equivalent to human Alport syndrome, to that from unaffected dogs. Additionally, we sought to characterize changes in relative mRNA expression of various genes associated with miR-21 function. miRNA was isolated from kidney tissue collected from both affected dogs and unaffected, age-matched littermates at defined milestones of disease progression, including end-stage renal disease (ESRD). Additionally, autopsy samples from affected dogs at ESRD and corresponding unaffected dogs were evaluated. Samples were scored based on histological changes, and relative expression of miR-21 and kidney disease-related genes was determined using quantitative real-time polymerase chain reaction. In affected dogs, significant upregulation of kidney miR-21 was first detected at the milestone corresponding with increased serum creatinine. Furthermore, miR-21 expression correlated significantly with urine protein: urine creatinine ratio, serum creatinine concentration, glomerular filtration rate, and histologic lesions (glomerular damage, tubular damage, chronic inflammation, and fibrosis). At end-stage disease, COL1A1, TGFB1 and its receptor, TGFB2, and Serpine1 were upregulated, while PPARA, PPARGC1A, ACADM, SOD1, and EGF were downregulated. In conclusion, miR-21 is abnormally upregulated in the kidneys of dogs with CKD caused by XLHN, which may play an important pathologic role in the progression of disease by dysregulating multiple pathways. |
| Databáze: | OpenAIRE |
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