Abstract: PO2016
Progranulin Deficiency Exacerbates High-Fat Diet-Induced Inflammation in Kidney
Session Information
- Health Maintenance, Nutrition, and Metabolism: Basic
October 22, 2020 | Location: On-Demand
Abstract Time: 10:00 AM - 12:00 PM
Category: Health Maintenance, Nutrition, and Metabolism
- 1300 Health Maintenance, Nutrition, and Metabolism
Authors
- Murakoshi, Maki, Department of Nephrology, Juntendo University Faculty of Medicine, Tokyo, Japan
- Gohda, Tomohito, Department of Nephrology, Juntendo University Faculty of Medicine, Tokyo, Japan
- Suzuki, Yusuke, Department of Nephrology, Juntendo University Faculty of Medicine, Tokyo, Japan
Background
Progranulin (PGRN) has been reported to bind to tumor necrosis factor (TNF) receptor (TNFR) and inhibit TNFα signals. Conversely, PGRN is a ‘bad’ adipokine that can contribute to insulin resistance in some metabolic diseases. We evaluated the effect of augmentation of TNFα signals by PGRN deficiency on the progression of kidney injury in high-fat diet-induced obesity model mice.
Methods
Eight-week-old PGRN knockout (KO) mice and their wild-type (WT) mice were fed a standard diet or high-fat diet (HFD) for 12 weeks. Mouse proximal tubule (mProx24) cells knocked down with PGRN siRNA were treated with TNFα stimulation.
Results
The body weight and albuminuria were significantly increased in WT-HFD group compared with WT-standard diet (SD) group. The body weight of KO-HFD group was significantly decreased compared with WT-HFD group. However, albuminuria and the expression of renal inflammatory markers including TNFα in KO-HFD group were increased than those in WT-HFD group. On the other hand, the WT-HFD mice showed vacuolization in the proximal tubule, but KO-HFD mice did not. Immunohistochemical analysis showed that vacuolar membranes were clearly positive for a lysosomal marker, LAMP-1, suggesting impairment in lysosomal function. The expression of megalin which plays a critical role in the reabsorption of protein in proximal tubules was found to be decreased in KO mice compared with WT mice, and also reduced in mProx stimulated with TNFα.
Conclusion
PGRN deficient exacerbated renal inflammation caused by high-fat diet, while the results also showed improvement in tubular vacuolation. Anti-inflammatory treatment with PGRN for kidney diseases should be considered based on the opposing function of PGRN.
Funding
- Private Foundation Support