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Kidney Week

Abstract: PO2016

Progranulin Deficiency Exacerbates High-Fat Diet-Induced Inflammation in Kidney

Session Information

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