1. Integrated miRNA–mRNA Analysis Reveals Critical miRNAs and Targets in Diet-Induced Obesity-Related Glomerulopathy.
- Author
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López-Martínez, Marina, Armengol, Maria Pilar, Pey, Irina, Farré, Xavier, Rodríguez-Martínez, Paula, Ferrer, Mireia, Porrini, Esteban, Luis-Lima, Sergio, Díaz-Martín, Laura, Rodríguez-Rodríguez, Ana Elena, Cruz-Perera, Coriolano, Alcalde, Marta, and Navarro-Díaz, Maruja
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OBESITY complications , *MICRORNA , *GENE expression , *LABORATORY rats , *HIGH-fat diet , *FAT - Abstract
This study aimed to investigate obesity-related glomerulopathy (ORG) at cellular, structural, and transcriptomic levels. Thirty Wistar rats were randomized into two groups: 15 rats were fed with a standard diet (SD-rats), and 15 rats were fed with a high-fat diet (HFD-rats). After 10 weeks, the weight, kidney function, histological features, and transcriptomic changes were assessed. HFD-rats gained significantly more weight (55.8% vs. 29.2%; p < 0.001) and albuminuria (10,384.04 ng/mL vs. 5845.45 ng/mL; p < 0.001) compared to SD-rats. HFD-rats exhibited early stages of ORG, with predominant mesangial matrix increase and podocyte hypertrophy (PH). These lesions correlated with differentially expressed (DE) genes and miRNAs. Functional analysis showed that miR-205, which was DE in both the kidneys and urine of HFD-rats, negatively regulated the PTEN gene, promoting lipid endocytosis in podocytes. The downregulation of PTEN was proved through a higher PTEN/nephrin ratio in the SD-rats and the presence of lipid vacuoles in HFD-podocytes. This study has found a specific targetome of miRNAs and gene expression in early stages of ORG. Also, it emphasizes the potential value of miR-205 as a urinary biomarker for detecting podocyte injury in ORG, offering a tool for early diagnosis, and opening new avenues for future therapeutic research of obesity-related glomerulopathy. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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