Vitamin D deficiency contributes to the diabetic kidney disease progression via increase ZEB1/ZEB2 expressions
Abstract Background Diabetic kidney disease (DKD) remains one of the main causes of end-stage renal disease (ESRD) and mortality in diabetic patients worldwide. Vitamin D deficiency (VitDD) is one of the main consequences of different chronic kidney disease (CKD) types and is associated with rapid p...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Publishing Group
2023-07-01
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| Series: | Nutrition & Diabetes |
| Online Access: | https://doi.org/10.1038/s41387-023-00238-2 |
| _version_ | 1827910473882796032 |
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| author | Cláudia Silva Souza Amanda Lima Deluque Beatriz Magalhães Oliveira Ana Lívia Dias Maciel Cleonice Giovanini Patrícia Aline Boer Francisco José Albuquerque de Paula Roberto Silva Costa Heloísa Della Colleta Franscecato Lucas Ferreira de Almeida Terezila Machado Coimbra |
| author_facet | Cláudia Silva Souza Amanda Lima Deluque Beatriz Magalhães Oliveira Ana Lívia Dias Maciel Cleonice Giovanini Patrícia Aline Boer Francisco José Albuquerque de Paula Roberto Silva Costa Heloísa Della Colleta Franscecato Lucas Ferreira de Almeida Terezila Machado Coimbra |
| author_sort | Cláudia Silva Souza |
| collection | DOAJ |
| description | Abstract Background Diabetic kidney disease (DKD) remains one of the main causes of end-stage renal disease (ESRD) and mortality in diabetic patients worldwide. Vitamin D deficiency (VitDD) is one of the main consequences of different chronic kidney disease (CKD) types and is associated with rapid progression to ESRD. Nevertheless, the mechanisms that lead to this process are poorly understood. This study aimed to characterize a model of diabetic nephropathy progression in VitDD and the epithelial-mesenchymal-transition (EMT) role in these processes. Methods Wistar Hannover rats received a diet with or without VitD before type 1 diabetes (T1D) induction. After this procedure, the rats were accompanied for 12 and 24 weeks after T1D induction and the renal function, structure, cell transdifferentiating markers and zinc finger e-box binding homeobox 1/2 (ZEB1/ZEB2) contribution to kidney damage were evaluated during the DKD progression. Results The results showed an increase in glomerular tuft, mesangial and interstitial relative areas and renal function impairment in VitD-deficient diabetic rats compared to diabetic rats that received a VitD-containing diet. These alterations can be associated with increased expression of EMT markers, ZEB1 gene expression, ZEB2 protein expression and TGF-β1 urinary excretion. Decreased miR-200b expression, an important post-transcriptional regulator of ZEB1 and ZEB2 was also observed. Conclusion Our data demonstrated that VitD deficiency contributes to the rapid development and progression of DKD in diabetic rats induced by increase ZEB1/ZEB2 expressions and miR-200b downregulation. |
| first_indexed | 2024-03-13T01:51:59Z |
| format | Article |
| id | doaj.art-d823c22d4a1f4a7dafb8698066bd105d |
| institution | Directory Open Access Journal |
| issn | 2044-4052 |
| language | English |
| last_indexed | 2024-03-13T01:51:59Z |
| publishDate | 2023-07-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Nutrition & Diabetes |
| spelling | doaj.art-d823c22d4a1f4a7dafb8698066bd105d2023-07-02T11:30:02ZengNature Publishing GroupNutrition & Diabetes2044-40522023-07-0113111110.1038/s41387-023-00238-2Vitamin D deficiency contributes to the diabetic kidney disease progression via increase ZEB1/ZEB2 expressionsCláudia Silva Souza0Amanda Lima Deluque1Beatriz Magalhães Oliveira2Ana Lívia Dias Maciel3Cleonice Giovanini4Patrícia Aline Boer5Francisco José Albuquerque de Paula6Roberto Silva Costa7Heloísa Della Colleta Franscecato8Lucas Ferreira de Almeida9Terezila Machado Coimbra10Department of Physiology of Ribeirao Preto Medical School, University of Sao PauloDepartment of Physiology of Ribeirao Preto Medical School, University of Sao PauloDepartment of Physiology of Ribeirao Preto Medical School, University of Sao PauloDepartment of Physiology of Ribeirao Preto Medical School, University of Sao PauloDepartment of Physiology of Ribeirao Preto Medical School, University of Sao PauloDepartment of Internal Medicine, Faculty of Medical Sciences, State University of CampinasDepartment of Internal Medicine of Ribeirao Preto Medical School, University of Sao PauloDepartment of Internal Medicine of Ribeirao Preto Medical School, University of Sao PauloDepartment of Physiology of Ribeirao Preto Medical School, University of Sao PauloDepartment of Physiology of Ribeirao Preto Medical School, University of Sao PauloDepartment of Physiology of Ribeirao Preto Medical School, University of Sao PauloAbstract Background Diabetic kidney disease (DKD) remains one of the main causes of end-stage renal disease (ESRD) and mortality in diabetic patients worldwide. Vitamin D deficiency (VitDD) is one of the main consequences of different chronic kidney disease (CKD) types and is associated with rapid progression to ESRD. Nevertheless, the mechanisms that lead to this process are poorly understood. This study aimed to characterize a model of diabetic nephropathy progression in VitDD and the epithelial-mesenchymal-transition (EMT) role in these processes. Methods Wistar Hannover rats received a diet with or without VitD before type 1 diabetes (T1D) induction. After this procedure, the rats were accompanied for 12 and 24 weeks after T1D induction and the renal function, structure, cell transdifferentiating markers and zinc finger e-box binding homeobox 1/2 (ZEB1/ZEB2) contribution to kidney damage were evaluated during the DKD progression. Results The results showed an increase in glomerular tuft, mesangial and interstitial relative areas and renal function impairment in VitD-deficient diabetic rats compared to diabetic rats that received a VitD-containing diet. These alterations can be associated with increased expression of EMT markers, ZEB1 gene expression, ZEB2 protein expression and TGF-β1 urinary excretion. Decreased miR-200b expression, an important post-transcriptional regulator of ZEB1 and ZEB2 was also observed. Conclusion Our data demonstrated that VitD deficiency contributes to the rapid development and progression of DKD in diabetic rats induced by increase ZEB1/ZEB2 expressions and miR-200b downregulation.https://doi.org/10.1038/s41387-023-00238-2 |
| spellingShingle | Cláudia Silva Souza Amanda Lima Deluque Beatriz Magalhães Oliveira Ana Lívia Dias Maciel Cleonice Giovanini Patrícia Aline Boer Francisco José Albuquerque de Paula Roberto Silva Costa Heloísa Della Colleta Franscecato Lucas Ferreira de Almeida Terezila Machado Coimbra Vitamin D deficiency contributes to the diabetic kidney disease progression via increase ZEB1/ZEB2 expressions Nutrition & Diabetes |
| title | Vitamin D deficiency contributes to the diabetic kidney disease progression via increase ZEB1/ZEB2 expressions |
| title_full | Vitamin D deficiency contributes to the diabetic kidney disease progression via increase ZEB1/ZEB2 expressions |
| title_fullStr | Vitamin D deficiency contributes to the diabetic kidney disease progression via increase ZEB1/ZEB2 expressions |
| title_full_unstemmed | Vitamin D deficiency contributes to the diabetic kidney disease progression via increase ZEB1/ZEB2 expressions |
| title_short | Vitamin D deficiency contributes to the diabetic kidney disease progression via increase ZEB1/ZEB2 expressions |
| title_sort | vitamin d deficiency contributes to the diabetic kidney disease progression via increase zeb1 zeb2 expressions |
| url | https://doi.org/10.1038/s41387-023-00238-2 |
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