Abstract: SA-PO509
The Potential Therapeutic Effect of Active Vitamin D Supplementation in Preventing Initiation and Progression of Diabetic Nephropathy in a Diabetic Mice Model
Session Information
- Diabetic Kidney Disease: Basic - III
November 09, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Diabetic Kidney Disease
- 601 Diabetic Kidney Disease: Basic
Authors
- Thawko, Tina, Diabetes &metabolism Lab Azrieli faculty of medicine, Lower Galilee, Israel
- Nakhoul, Nakhoul, Diabetes & Metabolism Lab Azrieli Faculty of Medicine, Ramat Gan, Israel
- Nakhoul, Rula, Szejed Faculty of Medicine Hungary, Szeged, Hungary
- Evgeny, Farber, Nephrology &Hypertension Division Baruch Padeh Poriya Medical Ctr, Lower Galilee, Israel
- Nakhoul, Farid M., Nephrology &Hypertension Division Baruch Padeh Poriya Medical Ctr, Lower Galilee, Israel
- Dahan, Inbal, Diabetes &metabolism Lab Azrieli faculty of medicine, Lower Galilee, Israel
Background
Diabetiv Nephropathy (DN) is characterized by morphological changes in podocytes and proximal tubule cells (PCT), and are characterized by hyperfiltration, albuminuria, glomerular sclerosis to ESRD. . DN mice suffer from an active vitamin D deficiency, which results in podocytopathy and PCT injury. We hypothesize that supplementation of active vitamin D paricalcitol(P) to DN mice may slow the development & progression of DN. .
Methods
Renal injury in diabetic mice with and without P treatment (TX), and control mice, were evaluated for albuminuria, blood Creatinine and BUN levels. The kidney biopsies were subjected to PAS & IHD staining: of vitamin D receptor (VDR) expression, villin, nephrin, podocin and fibronectin proteins. We used 4 groups of mice:(1) CON-wild type (2) DM group after DM induction with STZ were treated with vehicle for 12 weeks.(3) DM+P after STZ group - diabetic mice treated with P before the onset of DN, and one week after DM induction, i.p. 3 times a W for 12 wkss, (4) DM+P group - 3 weeks after diabetes induction, the mice were treated with P i.p. 3 times a W for 12 wks.
Results
1. VDR expression increased in DM+P after STZ (1.08±0.13) compared with DM+P group (0.59±0.13),
2, Renal villin expression of DM mice was significantly decreased (0.53±0.09) compared with control mice (1.14±0.05, p<0.001), but P TX before and after the onset of DN (DM+P and DM+P after STZ groups) restored villin expression,
3. P TX (DM+P and DM+P after STZ) decreased fibronectin expression.
4. Nephrin expression levels were decreased in DM group (0.5±0.11) compared with control group (1.03±0.09). P treatment (DM+P, DM+P after STZ) restore nephrin levels to normal (1.26±0.22) VS (0.99±0.04) respectively.
5. Renal expression of podocin was decreased in DM mice compared with control mice. P TX restore podocin expression in DM+P after STZ TX.
Conclusion
1. Significant protective effect of Paricalcitol treatment in preventing the initiation and progression of DN in STZ-induced diabetic mice mode.
2. Increasing the expression of VDR and restoration of nephrin-podocine proteins with decreasing fibronectin, , prevent the progression of DN
3. Our findings can be proposed as a new approach to deal with DM complications by selective Vitamin D supplementation in early stages of DN.
Funding
- Government Support - Non-U.S.