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A Quantitative Detection Method for MicroRNAs in the Kidney of an Ischemic Kidney Injury Mouse Model
Published on: September 11, 2020
microRNA Expression Profile in Obesity-Induced Kidney Disease Driven by High-Fat Diet in Mice
Àuria Eritja1, Maite Caus1, Thalia Belmonte2,3
1Vascular and Renal Translational Research Group, Biomedical Research Institute of Lleida Dr. Pifarré Foundation (IRBLleida), 25196 Lleida, Spain.
Abstract:
Obesity is one of the main causes of chronic kidney disease; however, the precise molecular mechanisms leading to the onset of kidney injury and dysfunction in obesity-associated nephropathy remain unclear. The present study aimed to unveil the kidney microRNA (miRNA) expression profile in a model of obesity-induced kidney disease in C57BL/6J mice using next-generation sequencing (NGS) analysis. High-fat diet (HFD)-induced obesity led to notable structural alterations in tubular and glomerular regions of the kidney, increased renal expression of proinflammatory and profibrotic genes, as well as an elevated renal expression of genes involved in cellular lipid metabolism. The miRNA sequencing analysis identified a set of nine miRNAs differentially expressed in the kidney upon HFD feeding, with miR-5099, miR-551b-3p, miR-223-3p, miR-146a-3p and miR-21a-3p showing the most significant differential expression between standard diet (STD) and HFD mice. A validation analysis showed that the expression levels of miR-5099, miR-551b-3p and miR-146a-3p were consistent with NGS results, while Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) enrichment analyses revealed that these three validated miRNAs modulated target genes involved in metabolic and adipocytokine pathways, fatty acid and lipid metabolism, and inflammatory, senescence and profibrotic pathways. Our results suggest that differentially expressed miRNAs play pivotal roles in the intricate pathophysiology of obesity-associated kidney disease and could potentially create novel treatment strategies to counteract the deleterious effects of obesity on kidney function.
Insights
Obesity causes kidney disease through unclear molecular pathways. This study identified key microRNAs (miRNAs) in mice kidneys affected by high-fat diets, revealing their role in metabolic and inflammatory processes.
Area of Science:
- Nephrology
- Molecular Biology
- Genomics
Background:
- Obesity is a major risk factor for chronic kidney disease (CKD).
- The molecular mechanisms underlying obesity-associated nephropathy are not fully understood.
- MicroRNAs (miRNAs) are implicated in various disease processes, including kidney injury.
Purpose of the Study:
- To investigate the kidney microRNA (miRNA) expression profile in a mouse model of obesity-induced kidney disease.
- To identify specific miRNAs involved in the pathophysiology of obesity-associated nephropathy.
- To explore the potential therapeutic targets for treating obesity-related kidney dysfunction.
Main Methods:
- Utilized a high-fat diet (HFD) model in C57BL/6J mice to induce obesity and kidney disease.
- Employed next-generation sequencing (NGS) for comprehensive miRNA expression profiling in kidney tissue.
- Performed validation analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) enrichment analyses on differentially expressed miRNAs.
Main Results:
- HFD induced structural kidney damage, increased pro-inflammatory and pro-fibrotic gene expression, and altered lipid metabolism genes.
- NGS identified nine differentially expressed miRNAs in the kidneys of HFD mice, with miR-5099, miR-551b-3p, and miR-146a-3p showing significant changes.
- Validated miRNAs target genes involved in metabolic, adipocytokine, lipid metabolism, inflammatory, senescence, and fibrotic pathways.
Conclusions:
- Differentially expressed miRNAs play critical roles in the complex mechanisms of obesity-associated kidney disease.
- These identified miRNAs represent potential novel therapeutic targets for mitigating obesity's detrimental effects on kidney function.
- Understanding miRNA involvement offers new avenues for developing treatment strategies for nephropathy in obese individuals.
