BlockingαVβ3 Integrin Ligand Occupancy Inhibits the Progression of Albuminuria in Diabetic Rats
This study determined if blocking ligand occupancy of the αVβ3 integrin could inhibit the pathophysiologic changes that occur in the early stages of diabetic nephropathy (DN). Diabetic rats were treated with either vehicle or a monoclonal antibody that binds the β3 subunit of the αVβ3 integrin. Afte...
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| Format: | Article |
| Language: | English |
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Wiley
2014-01-01
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| Series: | Journal of Diabetes Research |
| Online Access: | http://dx.doi.org/10.1155/2014/421827 |
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| _version_ | 1832568333702004736 |
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| author | Laura A. Maile Katherine Gollahon Christine Wai Paul Dunbar Walker Busby David Clemmons |
| author_facet | Laura A. Maile Katherine Gollahon Christine Wai Paul Dunbar Walker Busby David Clemmons |
| author_sort | Laura A. Maile |
| collection | DOAJ |
| description | This study determined if blocking ligand occupancy of the αVβ3 integrin could inhibit the pathophysiologic changes that occur in the early stages of diabetic nephropathy (DN). Diabetic rats were treated with either vehicle or a monoclonal antibody that binds the β3 subunit of the αVβ3 integrin. After 4 weeks of diabetes the urinary albumin to creatinine ratio (UACR) increased in both diabetic animals that subsequently received vehicle and in the animals that subsequently received the anti-β3 antibody compared with control nondiabetic rats. After 8 weeks of treatment the UACR continued to rise in the vehicle-treated rats; however it returned to levels comparable to control nondiabetic rats in rats treated with the anti-β3 antibody. Treatment with the antibody prevented the increase of several profibrotic proteins that have been implicated in the development of DN. Diabetes was associated with an increase in phosphorylation of the β3 subunit in kidney homogenates from diabetic animals, but this was prevented by the antibody treatment. This study demonstrates that, when administered after establishment of early pathophysiologic changes in renal function, the anti-β3 antibody reversed the effects of diabetes normalizing albuminuria and profibrotic proteins in the kidney to the levels observed in nondiabetic control animals. |
| format | Article |
| id | doaj-art-0951f397a7bd4bd98163ee2a114df569 |
| institution | Kabale University |
| issn | 2314-6745 2314-6753 |
| language | English |
| publishDate | 2014-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Diabetes Research |
| spelling | doaj-art-0951f397a7bd4bd98163ee2a114df5692025-02-03T00:59:14ZengWileyJournal of Diabetes Research2314-67452314-67532014-01-01201410.1155/2014/421827421827BlockingαVβ3 Integrin Ligand Occupancy Inhibits the Progression of Albuminuria in Diabetic RatsLaura A. Maile0Katherine Gollahon1Christine Wai2Paul Dunbar3Walker Busby4David Clemmons5Department of Medicine, UNC School of Medicine, Chapel Hill, NC 27599, USADepartment of Medicine, UNC School of Medicine, Chapel Hill, NC 27599, USADepartment of Medicine, UNC School of Medicine, Chapel Hill, NC 27599, USADepartment of Medicine, UNC School of Medicine, Chapel Hill, NC 27599, USADepartment of Medicine, UNC School of Medicine, Chapel Hill, NC 27599, USADepartment of Medicine, UNC School of Medicine, Chapel Hill, NC 27599, USAThis study determined if blocking ligand occupancy of the αVβ3 integrin could inhibit the pathophysiologic changes that occur in the early stages of diabetic nephropathy (DN). Diabetic rats were treated with either vehicle or a monoclonal antibody that binds the β3 subunit of the αVβ3 integrin. After 4 weeks of diabetes the urinary albumin to creatinine ratio (UACR) increased in both diabetic animals that subsequently received vehicle and in the animals that subsequently received the anti-β3 antibody compared with control nondiabetic rats. After 8 weeks of treatment the UACR continued to rise in the vehicle-treated rats; however it returned to levels comparable to control nondiabetic rats in rats treated with the anti-β3 antibody. Treatment with the antibody prevented the increase of several profibrotic proteins that have been implicated in the development of DN. Diabetes was associated with an increase in phosphorylation of the β3 subunit in kidney homogenates from diabetic animals, but this was prevented by the antibody treatment. This study demonstrates that, when administered after establishment of early pathophysiologic changes in renal function, the anti-β3 antibody reversed the effects of diabetes normalizing albuminuria and profibrotic proteins in the kidney to the levels observed in nondiabetic control animals.http://dx.doi.org/10.1155/2014/421827 |
| spellingShingle | Laura A. Maile Katherine Gollahon Christine Wai Paul Dunbar Walker Busby David Clemmons BlockingαVβ3 Integrin Ligand Occupancy Inhibits the Progression of Albuminuria in Diabetic Rats Journal of Diabetes Research |
| title | BlockingαVβ3 Integrin Ligand Occupancy Inhibits the Progression of Albuminuria in Diabetic Rats |
| title_full | BlockingαVβ3 Integrin Ligand Occupancy Inhibits the Progression of Albuminuria in Diabetic Rats |
| title_fullStr | BlockingαVβ3 Integrin Ligand Occupancy Inhibits the Progression of Albuminuria in Diabetic Rats |
| title_full_unstemmed | BlockingαVβ3 Integrin Ligand Occupancy Inhibits the Progression of Albuminuria in Diabetic Rats |
| title_short | BlockingαVβ3 Integrin Ligand Occupancy Inhibits the Progression of Albuminuria in Diabetic Rats |
| title_sort | blockingαvβ3 integrin ligand occupancy inhibits the progression of albuminuria in diabetic rats |
| url | http://dx.doi.org/10.1155/2014/421827 |
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