Abstract: FR-PO599
FK506 Attenuates Proteinuria by Inhibiting Endothelial-to-Mesenchymal Transition in Rats with Diabetic Nephropathy
Session Information
- Diabetes Mellitus and Obesity: Basic - Experimental - II
November 03, 2017 | Location: Hall H, Morial Convention Center
Abstract Time: 10:00 AM - 10:00 AM
Category: Diabetes
- 501 Diabetes Mellitus and Obesity: Basic - Experimental
Author
- Song, Kaiyun, Southeast University School of Medicine, Nanjing, China
Background
Many studies have shown that endothelial cell damage is present in the early stage of diabetic nephropathy(DN) and endothelium-podocytes crosstalk plays an important role in DN. FK506 was found to be beneficial for attenuating proteinuria in DN recently. However, the underlying mechanism is still unknown. In this study, we investigated whether endothelial-to-mesenchymal transition(EndMT) of DN could be attenuated by FK506.
Methods
Thirty-six SD rats were randomly divided into three groups(n=12/group): control group, DN group, FK506 treatment group. The DN model was established using strephozotocin(58mg/kg). The diabetic rats were administered with FK506 by gavage (0.15mg/kg/d) for 34 weeks. Some biochemical parameters, urinary albumin (UAL), and kidney weight/body weight (KW/BW) were measured. Nephrin and podocin were detected by Western blotting(WB) and Endothelial marker (CD31), FSP1 and α-SMA were detected by Double immunofluorescence staining, immunohistochemistry, real time-PCR and WB.
Results
There were significant increases in the levels of SCr, BUN, KW/BW, UAL, the glomerular volume, proliferative mesangial cells, width of the mesangial area in DN. However, these were reduced by FK506 treatment , compared with DN (P<0.05). Disorder, widening and fusion of podocyte processes were observed under the electron microscope in DN and they were reduced by FK506 treatment (P<0.05). The results of the WB showed that the expression of nephrin and podocin decreased in DN compared with the control and was significantly improved by FK506 treatment (P<0.05). Double immunofluorescence staining, Immunohistochemistry, real time-PCR and WB showed that the expression level of CD31 was downregulated in DN, whereas the expressions of FSP1, α-SMA were markedly upregulated. These changes were inhibited by FK506 treatment (P<0.05).
Conclusion
The results might provide a novel insight FK506 could attenuate the proteinuria by inhibiting endothelium-podocytes crosstalk in rats with DN. These results still need further study.
Funding
- Government Support - Non-U.S.