Abstract: TH-PO200
IL-34 Mediate the Development of Diabetic Nephropathy by Promoting Macrophage Infiltration
Session Information
- Diabetic Kidney Disease: Basic - I
November 03, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
Abstract Time: 10:00 AM - 12:00 PM
Category: Diabetic Kidney Disease
- 601 Diabetic Kidney Disease: Basic
Authors
- Ning, Wang Yi, Peking Union Medical College Hospital, Dongcheng-qu, Beijing, China
- Zheng, Ke, Peking Union Medical College Hospital, Dongcheng-qu, Beijing, China
- Wang, Gangan, Peking Union Medical College Hospital, Dongcheng-qu, Beijing, China
- Mei, Li Xue, Peking Union Medical College Hospital, Dongcheng-qu, Beijing, China
Background
Diabetic nephropathy (DN) is the leading cause of end-stage renal disease around the world. Macrophages contribute to the development of renal injury and sclerosis. IL-34, expressed by tubular epithelial cells (TECs), promotes macrophage survival and proliferation by binding to the cFMS receptor and PTPRZ receptor on macrophages in SLE and AKI. The role of IL-34 in diabetic nephropathy and its effect on the quantification and polarization of macrophages have not been elucidated.
Methods
To validate the role of IL-34 in diabetes kidney disease, we established progressive diabetes nephropathy by unilateral nephrectomy combined with a 60% high-fat diet and STZ (120mg/kg) injection(Unx+60%HFD+STZ) based on WT and IL-34 KO mice respectively. Meanwhile, the sham operation group was used as the experimental control group. After 16 weeks of injection with STZ，we collected the kidney samples to evaluate the injury extent of the kidney, and flow cytometry was used to evaluate the quantification and polarization direction of macrophages.
Results
In vivo, compared with the sham group, the mRNA level of IL-34 in kidney tissue was significantly up-regulated in WT-Unx+60%HFD+STZ. The result of HE staining and PAS staining showed that under the circumstance of unilateral nephrectomy model of high fat, IL-34 KO mice present less renal tissue pathological injure than WT mice. IL-34 KO-Unx+60%HFD+STZ mice had less infiltration of macrophages than WT - Unx+60%HFD+STZ renal tissue.
Conclusion
IL-34 accelerates the progression of diabetes by promoting macrophage infiltration, targeting IL-34 knockout can delay the progression of diabetic nephropathy.
Funding
- Government Support – Non-U.S.