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Glomerulopathy in the KK.Cg-A(y)/J Mouse Reflects the Pathology of Diabetic Nephropathy
The KK.Cg-A (y)/J (KK-A (y)) mouse strain is a previously described model of type 2 diabetes with renal impairment. In the present study, female KK-A (y) mice received an elevated fat content diet (24% of calories), and a cohort was uninephrectomized (Unx) to drive renal disease severity. Compared t...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Hindawi Publishing Corporation
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3655591/ https://www.ncbi.nlm.nih.gov/pubmed/23710468 http://dx.doi.org/10.1155/2013/498925 |
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author | O'Brien, Stephen P. Smith, Mandy Ling, Hong Phillips, Lucy Weber, William Lydon, John Maloney, Colleen Ledbetter, Steven Arbeeny, Cynthia Wawersik, Stefan |
author_facet | O'Brien, Stephen P. Smith, Mandy Ling, Hong Phillips, Lucy Weber, William Lydon, John Maloney, Colleen Ledbetter, Steven Arbeeny, Cynthia Wawersik, Stefan |
author_sort | O'Brien, Stephen P. |
collection | PubMed |
description | The KK.Cg-A (y)/J (KK-A (y)) mouse strain is a previously described model of type 2 diabetes with renal impairment. In the present study, female KK-A (y) mice received an elevated fat content diet (24% of calories), and a cohort was uninephrectomized (Unx) to drive renal disease severity. Compared to KK-a/a controls, 26-week-old KK-A (y) mice had elevated HbA1c, insulin, leptin, triglycerides, and cholesterol, and Unx further elevated these markers of metabolic dysregulation. Unx KK-A (y) mice also exhibited elevated serum BUN and reduced glomerular filtration, indicating that reduction in renal mass leads to more severe impairment in renal function. Glomerular hypertrophy and hypercellularity, mesangial matrix expansion, podocyte effacement, and basement membrane thickening were present in both binephric and uninephrectomized cohorts. Glomerular size was increased in both groups, but podocyte density was reduced only in the Unx animals. Consistent with functional and histological evidence of increased injury, fibrotic (fibronectin 1, MMP9, and TGFβ1) and inflammatory (IL-6, CD68) genes were markedly upregulated in Unx KK-A (y) mice, while podocyte markers (nephrin and podocin) were significantly decreased. These data suggest podocyte injury developing into glomerulopathy in KK-A (y) mice. The addition of uninephrectomy enhances renal injury in this model, resulting in a disease which more closely resembles human diabetic nephropathy. |
format | Online Article Text |
id | pubmed-3655591 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Hindawi Publishing Corporation |
record_format | MEDLINE/PubMed |
spelling | pubmed-36555912013-05-24 Glomerulopathy in the KK.Cg-A(y)/J Mouse Reflects the Pathology of Diabetic Nephropathy O'Brien, Stephen P. Smith, Mandy Ling, Hong Phillips, Lucy Weber, William Lydon, John Maloney, Colleen Ledbetter, Steven Arbeeny, Cynthia Wawersik, Stefan J Diabetes Res Research Article The KK.Cg-A (y)/J (KK-A (y)) mouse strain is a previously described model of type 2 diabetes with renal impairment. In the present study, female KK-A (y) mice received an elevated fat content diet (24% of calories), and a cohort was uninephrectomized (Unx) to drive renal disease severity. Compared to KK-a/a controls, 26-week-old KK-A (y) mice had elevated HbA1c, insulin, leptin, triglycerides, and cholesterol, and Unx further elevated these markers of metabolic dysregulation. Unx KK-A (y) mice also exhibited elevated serum BUN and reduced glomerular filtration, indicating that reduction in renal mass leads to more severe impairment in renal function. Glomerular hypertrophy and hypercellularity, mesangial matrix expansion, podocyte effacement, and basement membrane thickening were present in both binephric and uninephrectomized cohorts. Glomerular size was increased in both groups, but podocyte density was reduced only in the Unx animals. Consistent with functional and histological evidence of increased injury, fibrotic (fibronectin 1, MMP9, and TGFβ1) and inflammatory (IL-6, CD68) genes were markedly upregulated in Unx KK-A (y) mice, while podocyte markers (nephrin and podocin) were significantly decreased. These data suggest podocyte injury developing into glomerulopathy in KK-A (y) mice. The addition of uninephrectomy enhances renal injury in this model, resulting in a disease which more closely resembles human diabetic nephropathy. Hindawi Publishing Corporation 2013 2013-04-24 /pmc/articles/PMC3655591/ /pubmed/23710468 http://dx.doi.org/10.1155/2013/498925 Text en Copyright © 2013 Stephen P. O'Brien et al. https://creativecommons.org/licenses/by/3.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article O'Brien, Stephen P. Smith, Mandy Ling, Hong Phillips, Lucy Weber, William Lydon, John Maloney, Colleen Ledbetter, Steven Arbeeny, Cynthia Wawersik, Stefan Glomerulopathy in the KK.Cg-A(y)/J Mouse Reflects the Pathology of Diabetic Nephropathy |
title | Glomerulopathy in the KK.Cg-A(y)/J Mouse Reflects the Pathology of Diabetic Nephropathy |
title_full | Glomerulopathy in the KK.Cg-A(y)/J Mouse Reflects the Pathology of Diabetic Nephropathy |
title_fullStr | Glomerulopathy in the KK.Cg-A(y)/J Mouse Reflects the Pathology of Diabetic Nephropathy |
title_full_unstemmed | Glomerulopathy in the KK.Cg-A(y)/J Mouse Reflects the Pathology of Diabetic Nephropathy |
title_short | Glomerulopathy in the KK.Cg-A(y)/J Mouse Reflects the Pathology of Diabetic Nephropathy |
title_sort | glomerulopathy in the kk.cg-a(y)/j mouse reflects the pathology of diabetic nephropathy |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3655591/ https://www.ncbi.nlm.nih.gov/pubmed/23710468 http://dx.doi.org/10.1155/2013/498925 |
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