The Therapeutic Effect of Active Vitamin D Supplementation in Preventing the Progression of Diabetic Nephropathy in a Diabetic Mouse Model
Background. Diabetic nephropathy (DN) is one of the most common microvascular complications of diabetes and is the leading cause of end-stage renal disease (ESRD) and replacement therapy worldwide. Vitamin D levels in DN patients are very low due to the decrease in the synthesis and activity of 1-α...
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Wiley
2020-01-01
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| Series: | Journal of Diabetes Research |
| Online Access: | http://dx.doi.org/10.1155/2020/7907605 |
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| author | Nakhoul Nakhoul Tina Thawko Evgeny Farber Inbal Dahan Hagar Tadmor Rola Nakhoul Anaam Hanut Ghasan Salameh Ibrahim Shagrawy Farid Nakhoul |
| author_facet | Nakhoul Nakhoul Tina Thawko Evgeny Farber Inbal Dahan Hagar Tadmor Rola Nakhoul Anaam Hanut Ghasan Salameh Ibrahim Shagrawy Farid Nakhoul |
| author_sort | Nakhoul Nakhoul |
| collection | DOAJ |
| description | Background. Diabetic nephropathy (DN) is one of the most common microvascular complications of diabetes and is the leading cause of end-stage renal disease (ESRD) and replacement therapy worldwide. Vitamin D levels in DN patients are very low due to the decrease in the synthesis and activity of 1-α hydroxylase in the proximal tubule cells and decrease in the vitamin D receptor abundance. To date, few studies have shown the antioxidant effects of 1α,25-dihydroxyvitamin D3 [1,25(OH)2D3] on hyperglycemia-induced renal injury. The selective activator of the vitamin D receptor, paricalcitol, reduces proteinuria and slows the progression of kidney injury. The precise mechanism through which vitamin D affects diabetic status and provides kidney protection remains to be determined. Methods. Diabetes mellitus (DM) was induced in 94 8-week-old DBA/2J mice by intraperitoneal injection of streptozotocin (STZ). DM mice were randomly divided into receiving vehicle or treatment with paricalcitol, the active vitamin D analog, 1 week after DM induction or paricalcitol treatment 3 weeks after DM induction. An additional control group of healthy wild-type mice was not treated. Urine albumin, blood urea nitrogen, and creatinine levels were measured before and at the end of the paricalcitol treatment. Periodic acid-Schiff, immunohistochemistry staining, and western blot of the renal tissues of vitamin D receptor, villin, nephrin, and podocin expressions, were analyzed. Results. Paricalcitol treatment restored villin, nephrin, and podocin protein levels that were downregulated upon DM induction, and reduced fibronectin protein level. Vitamin D receptor activation by paricalcitol may reduce proteinuria of DN in mice and alleviate high-glucose-induced injury of kidney podocytes by regulating the key molecules such nephrin-podocin. Conclusions. Paricalcitol treatment was associated with improved structural changes in type 1 diabetic mice including upregulation of vitamin D receptor expression, and decreased fibrosis markers such as fibronectin. These effects may contribute to the consistent benefit of vitamin D analog to slow the deterioration in glomerular function and reduce the risk of ESRD in patients with type 1 and 2 diabetes mellitus. Our results suggest that additional use of paricalcitol may be beneficial in treating patients with diabetes under standard therapeutic strategies. |
| format | Article |
| id | doaj-art-01f70d930baf42d68a304a38bcfeb7c7 |
| institution | OA Journals |
| issn | 2314-6745 2314-6753 |
| language | English |
| publishDate | 2020-01-01 |
| publisher | Wiley |
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| series | Journal of Diabetes Research |
| spelling | doaj-art-01f70d930baf42d68a304a38bcfeb7c72025-08-20T02:01:46ZengWileyJournal of Diabetes Research2314-67452314-67532020-01-01202010.1155/2020/79076057907605The Therapeutic Effect of Active Vitamin D Supplementation in Preventing the Progression of Diabetic Nephropathy in a Diabetic Mouse ModelNakhoul Nakhoul0Tina Thawko1Evgeny Farber2Inbal Dahan3Hagar Tadmor4Rola Nakhoul5Anaam Hanut6Ghasan Salameh7Ibrahim Shagrawy8Farid Nakhoul9The Diabetes & Metabolism Lab, Baruch Padeh Poriya Medical Center, Lower Galilee, IsraelThe Diabetes & Metabolism Lab, Baruch Padeh Poriya Medical Center, Lower Galilee, IsraelNephrology & Hypertension Division, Baruch Padeh Poriya Medical Center, Lower Galilee, IsraelThe Diabetes & Metabolism Lab, Baruch Padeh Poriya Medical Center, Lower Galilee, IsraelThe Diabetes & Metabolism Lab, Baruch Padeh Poriya Medical Center, Lower Galilee, IsraelSzeged Faculty of Medicine, Szeged, HungaryNephrology & Hypertension Division, Bar-Ilan University, Ramat Gan, IsraelThe Diabetes & Metabolism Lab, Baruch Padeh Poriya Medical Center, Lower Galilee, IsraelPathology Division, Baruch Padeh Poriya Medical Center, Lower Galilee, IsraelThe Diabetes & Metabolism Lab, Baruch Padeh Poriya Medical Center, Lower Galilee, IsraelBackground. Diabetic nephropathy (DN) is one of the most common microvascular complications of diabetes and is the leading cause of end-stage renal disease (ESRD) and replacement therapy worldwide. Vitamin D levels in DN patients are very low due to the decrease in the synthesis and activity of 1-α hydroxylase in the proximal tubule cells and decrease in the vitamin D receptor abundance. To date, few studies have shown the antioxidant effects of 1α,25-dihydroxyvitamin D3 [1,25(OH)2D3] on hyperglycemia-induced renal injury. The selective activator of the vitamin D receptor, paricalcitol, reduces proteinuria and slows the progression of kidney injury. The precise mechanism through which vitamin D affects diabetic status and provides kidney protection remains to be determined. Methods. Diabetes mellitus (DM) was induced in 94 8-week-old DBA/2J mice by intraperitoneal injection of streptozotocin (STZ). DM mice were randomly divided into receiving vehicle or treatment with paricalcitol, the active vitamin D analog, 1 week after DM induction or paricalcitol treatment 3 weeks after DM induction. An additional control group of healthy wild-type mice was not treated. Urine albumin, blood urea nitrogen, and creatinine levels were measured before and at the end of the paricalcitol treatment. Periodic acid-Schiff, immunohistochemistry staining, and western blot of the renal tissues of vitamin D receptor, villin, nephrin, and podocin expressions, were analyzed. Results. Paricalcitol treatment restored villin, nephrin, and podocin protein levels that were downregulated upon DM induction, and reduced fibronectin protein level. Vitamin D receptor activation by paricalcitol may reduce proteinuria of DN in mice and alleviate high-glucose-induced injury of kidney podocytes by regulating the key molecules such nephrin-podocin. Conclusions. Paricalcitol treatment was associated with improved structural changes in type 1 diabetic mice including upregulation of vitamin D receptor expression, and decreased fibrosis markers such as fibronectin. These effects may contribute to the consistent benefit of vitamin D analog to slow the deterioration in glomerular function and reduce the risk of ESRD in patients with type 1 and 2 diabetes mellitus. Our results suggest that additional use of paricalcitol may be beneficial in treating patients with diabetes under standard therapeutic strategies.http://dx.doi.org/10.1155/2020/7907605 |
| spellingShingle | Nakhoul Nakhoul Tina Thawko Evgeny Farber Inbal Dahan Hagar Tadmor Rola Nakhoul Anaam Hanut Ghasan Salameh Ibrahim Shagrawy Farid Nakhoul The Therapeutic Effect of Active Vitamin D Supplementation in Preventing the Progression of Diabetic Nephropathy in a Diabetic Mouse Model Journal of Diabetes Research |
| title | The Therapeutic Effect of Active Vitamin D Supplementation in Preventing the Progression of Diabetic Nephropathy in a Diabetic Mouse Model |
| title_full | The Therapeutic Effect of Active Vitamin D Supplementation in Preventing the Progression of Diabetic Nephropathy in a Diabetic Mouse Model |
| title_fullStr | The Therapeutic Effect of Active Vitamin D Supplementation in Preventing the Progression of Diabetic Nephropathy in a Diabetic Mouse Model |
| title_full_unstemmed | The Therapeutic Effect of Active Vitamin D Supplementation in Preventing the Progression of Diabetic Nephropathy in a Diabetic Mouse Model |
| title_short | The Therapeutic Effect of Active Vitamin D Supplementation in Preventing the Progression of Diabetic Nephropathy in a Diabetic Mouse Model |
| title_sort | therapeutic effect of active vitamin d supplementation in preventing the progression of diabetic nephropathy in a diabetic mouse model |
| url | http://dx.doi.org/10.1155/2020/7907605 |
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