Abstract: PO0646
Endogenous Interleukin 33 Contributes to the Progression of Diabetic Nephropathy
Session Information
- Diabetic Kidney Disease: Basic - I
November 04, 2021 | Location: On-Demand, Virtual Only
Abstract Time: 10:00 AM - 12:00 PM
Category: Diabetic Kidney Disease
- 601 Diabetic Kidney Disease: Basic
Author
- Zhu, Zixuan, Peking Union Medical College Hospital, Dongcheng-qu, Beijing, China
Background
Inflammation and fibrosis play a crucial role throughout the course of Diabetic Nephropathy (DN). Interleukin 33 (IL-33) is an early alarmin for inflammatory damage and also shows a relationship with fibrosis in multiple organs. However, it was little discussed in the field of chronic kidney disease. Here, we try to explore the role of IL-33 in DN.
Methods
21 patients with DN diagnosed by renal biopsy were retrospectively included; 6 kidney tissue adjacent to carcinomawere were collected as normal kidney samples; 5 healthy controls were included. IL-33 levels in serum and urine were measured and IL-33 of renal tissue were evaluated. db/db mice were used as an animal model to evaluate the IL-33 expression in the early stage of DN. IL-33KO mice with STZ injection combined with unilateral nephrectomy were used as an animal model to explore the regulatory effect of endogenous IL-33.
Results
In human samples, DN group showed a significantly higher level of IL-33 than that in the normal kidney tissue (P<0.0001). And the level was positively related to the degree of kidney fibrosis(Spearman’s ρ=0.072，P=0.007). The expression pattern of IL-33 in DN is different from that in normal condition. Further immunofluorescence staining suggested that IL-33 is expressed mainly by fibroblasts in the kidney of DN. And IL-33 level in DN group was also showed a higher level in urine (P=0.017). In animal models, IL-33 increased in the kidney of db/db group compared with db/m (P=0.011) during the early stage of DN, which was before the decrease of renal function and appearance of pathological lesions. In the IL-33 knockout mouse of STZ-induced diabetes combined with unilateral nephrectomy, the 32 weeks old IL-33KO group had lower blood glucose levels (P<0.001), reduced urinary albumin/creatinine level than (P=0.021) wild type group with diabetes. Staining of renal tissue also showed severe tubulointerstitial fibrosis, inflammatory cell infiltration, and glomerular mesangial expansion in wild type group, all of which were significantly attenuated in the IL-33KO group.
Conclusion
IL-33 is involved throughout the course of DN. The increase of IL-33 may play as an early warning factor in the disease and may participate in aggravating diabetic nephropathy by mediating the process of fibrosis. Based on our findings, IL-33 may have the potential to be a target for further mechanism research and treatment of DN.