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Obesity-related glomerulopathy is associated with elevated WT1 expression in podocytes
Sneha Jakhotia1, Rajesh Kavvuri2, Sumathi Raviraj2
1Department of Biochemistry, ICMR-National Institute of Nutrition, Hyderabad, 500007, TS, India.
Obesity significantly increases chronic kidney disease (CKD) risk. This study found elevated WT1 expression in kidney podocytes of obese animal models and human CKD patients, suggesting a novel role in obesity-related glomerulopathy (ORG) pathogenesis.
Area of Science:
- Nephrology
- Molecular Biology
- Obesity Research
Background:
- Obesity is a major global health concern, escalating the incidence of cardiovascular, metabolic diseases, and chronic kidney disease (CKD).
- Obesity-related glomerulopathy (ORG) and kidney dysfunction are linked to hemodynamic, metabolic, and lipotoxic factors, but precise mechanisms remain unclear.
Purpose of the Study:
- To investigate the molecular mechanisms driving obesity-related glomerulopathy (ORG).
- To explore the role of WT1 in the pathogenesis of kidney disease associated with obesity.
Main Methods:
- Utilized spontaneous obese WNIN/Ob rats and high-fat diet-induced obese mice models.
- Assessed kidney function, glomerular structure, and podocyte morphology.
- Analyzed gene expression in rodents and compared with human CKD patient data via Nephroseq and Kidney Precision Medicine Project databases.
Main Results:
- Both obese rat and mouse models exhibited proteinuria and glomerular deformities, including glomerulosclerosis and podocyte injury.
- Elevated expression of the transcription factor WT1 was observed in podocytes of obese models and human CKD patients.
- Altered expression of WT1 targets suggests WT1 induces a podocyte mesenchymal phenotype.
Conclusions:
- Elevated WT1 expression in adult podocytes is a novel finding in obesity-related kidney disease.
- WT1 may play a significant role in the pathogenesis of obesity-related glomerulopathy (ORG).
- Further research is needed to elucidate the exact mechanisms of WT1 induction and its specific role in podocyte dysfunction.
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