Abstract: PO1202
Wheat-Gluten Diet Attenuates Ccl2-Mediated Immune Response and Slows Polycystic Kidney Disease
Session Information
- Cystic Kidney Disease - I
November 04, 2021 | Location: On-Demand, Virtual Only
Abstract Time: 10:00 AM - 12:00 PM
Category: Genetic Diseases of the Kidneys
- 1001 Genetic Diseases of the Kidneys: Cystic
Authors
- Huang, Jifeng, The University of Alabama at Birmingham, Birmingham, Alabama, United States
- Yamaguchi, Shinobu, The University of Alabama at Birmingham, Birmingham, Alabama, United States
- Hsu, Jung-Shan, The University of Alabama at Birmingham, Birmingham, Alabama, United States
- Saigusa, Takamitsu, The University of Alabama at Birmingham, Birmingham, Alabama, United States
Group or Team Name
- Department of Medicine, Division of Nephrology
Background
Disease severity of autosomal-dominant polycystic kidney disease (ADPKD) is highly variable, even among families with the same gene mutation. A high protein diet is a well-recognized ADPKD progression-accelerating factor. Dietary protein composition is important, as pre-clinical studies have shown a soy protein-based diet slows kidney cyst formation in rodent PKD models. Recruitment of macrophages in the kidney are known to promote cystogenesis in PKD. We hypothesize that type of protein in the diet may serve as a potential environmental stimulant to immune response and cyst growth.
Methods
Using tamoxifen-inducible Pkd1-global knockout mice, we fed the mice with either a high casein-protein (animal-based protein: 60%), a low casein-protein (6%) or a high wheat-gluten (plant-based protein: 60%) for a total of 1 week or 6 weeks. Some mice fed a high casein protein diet were treated with liposomal clodronate or saline for a total of 5 weeks. Mice were euthanized and kidney cyst area, number of macrophages and chemokine/cytokine levels were measured.
Results
Pkd1-knockout mice fed a high casein diet increased the number of kidney macrophages, expression of macrophage-recruiting chemokine Ccl2 (but not chemokines Csf1 or Ccl5), pro-inflammatory cytokine (Il6, Tnf-a) and accelerated cyst growth compared to counterparts fed an iso-caloric high wheat-gluten (WG) diet or a low casein protein diet. We found that in very early stages during dietary casein load (1 week after diet modification), cyst expansion precedes macrophage recruitment in the kidney, indicating that diet per se triggers early cyst growth rather than as a consequence of macrophage recruitment and inflammation. High casein protein diet fed Pkd1-knockout mice treated with liposomal clodronate, resulted in decreased number of macrophages, cytokine and fewer cysts.
Conclusion
Wheat-gluten diet fed Pkd1-knockout mice resulted in decreased the number of macrophages, suppressed levels of kidney Ccl2, but not Csf1 or Ccl5, and slowed cyst growth compared to counterparts fed an isocaloric casein based diet. Dietary protein modification may suppress immune response and cyst growth in PKD.
Funding
- NIDDK Support