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| Status |
Public on Mar 17, 2022 |
| Title |
miRNAs in age-dependent renal impairment |
| Organism |
Mus musculus |
| Experiment type |
Non-coding RNA profiling by array
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| Summary |
Background: Age-dependent renal impairment contributes to renal dysfunction in both the general population and young and middle-aged patients with renal diseases. Pathological changes in age-dependent renal impairment include glomerulosclerosis and tubulointerstitial fibrosis. The molecules involved in age-dependent renal impairment are not fully elucidated. MicroRNA (miRNA) species were reported to modulate various renal diseases, but the miRNA species involved in age-dependent renal impairment are unclear. Here, we investigated miRNAs in age-dependent renal impairment, and we evaluated their potential as biomarkers and therapeutic targets.
Methods: We conducted an initial microarray profiling analysis to screen miRNAs whose expression levels changed in kidneys of senescence-accelerated resistant (SAMR1)-10-week-old (wk) mice and SAMR1-50wk mice and senescence-accelerated prone (SAMP1)-10wk mice and SAMP1-50wk mice. We then evaluated the expressions of differentially expressed miRNAs in serum from 13 older patients (>65 years old) with age-dependent renal impairment (estimated glomerular filtration ratio <60 mL/min/1.73 m2) by a quantitative real-time polymerase chain reaction (qRT-PCR) and compared the expressions with those of age-matched subjects with normal renal function. We also administered miRNA mimics or inhibitors (5 nmol) with a nonviral vector (polyethylenimine nanoparticles: PEI-NPs) to SAMP1-20wk mice to investigate the therapeutic effects.
Results: The qRT-PCR revealed a specific miRNA (miRNA-503-5p) whose level was significantly changed in SAMP1-50wk mouse kidneys in comparison to the controls. The expression level of miRNA-503-5p was upregulated in the serum of the 13 patients with age-dependent renal impairment compared to the age-matched subjects with normal renal function. The administration of a miRNA-503-5p-inhibitor with PEI-NPs decreased the miRNA-503-5p expression levels, resulting in the inhibition of renal fibrosis in mice via an inhibition of a pro-fibrotic signaling pathway and a suppression of glomerulosclerosis in mice by inhibiting intrinsic signaling pathways.
Conclusion: miRNA-503-5p may represent a biomarker for age-dependent renal impairment, and the inhibition of miRNA-503-5p had no effect on age-dependent renal impairment. However, the inhibition of miRNA-503-5p had therapeutic effects on renal fibrosis and glomerulosclerosis.
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| Overall design |
10-week-old SAMR1 mice (n=4), 50-week-old SAMR1 mice (n=4), 10-week-old SAMP1 mice (n=4), 50-week-old SAMP1 mice (n=4)
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| Contributor(s) |
Yanai K |
| Citation(s) |
35646947 |
| |
| Submission date |
Mar 16, 2022 |
| Last update date |
Jun 16, 2022 |
| Contact name |
Katsunori Yanai |
| E-mail(s) |
yanai03310751@yahoo.co.jp
|
| Organization name |
Jichi Medical University, Saitama Medical Center
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| Street address |
1-847, Amanuma-cho, Omiya-ku
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| City |
Saitama City |
| ZIP/Postal code |
330-8503 |
| Country |
Japan |
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| Platforms (1) |
| GPL21265 |
Agilent-070155 Mouse miRNA Microarray (miRBase Release 21.0, miRNA ID version) |
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| Samples (16)
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| Relations |
| BioProject |
PRJNA816716 |
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