Document Detail


Blocking Ligand Occupancy of the αVβ3 Integrin Inhibits the Development of Nephropathy in Diabetic Pigs.
MedLine Citation:
PMID:  25171599     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
Hyperglycemia stimulates secretion of αVβ3 ligands from vascular cells, including endothelial cells, resulting in activation of the αVβ3 integrin. This study determined whether blocking ligand occupancy of αVβ3 would inhibit the development of diabetic nephropathy. Ten diabetic pigs received an F(ab)2 fragment of an antibody directed against the extracellular domain of the β3-subunit, and 10 received a control IgG F(ab)2 for 18 weeks. Nondiabetic pigs excreted 115 ± 50 μg of protein/mg creatinine compared with control F(ab)2-treated diabetic animals (218 ± 57 μg/mg), whereas diabetic animals treated with the anti-β3 F(ab)2 excreted 119 ± 55 μg/mg (P < .05). Mesangial volume/glomerular volume increased to 21 ± 2.4% in control-treated diabetic animals compared with 14 ± 2.8% (P < .01) in animals treated with active antibody. Diabetic animals treated with control F(ab)2 had significantly less glomerular podocin staining compared with nondiabetic animals, and this decrease was attenuated by treatment with anti-β3 F(ab)2. Glomerular basement membrane thickness was increased in the control, F(ab)2-treated diabetic animals (212 ± 14 nm) compared with nondiabetic animals (170 ± 8.8 nm), but it was unchanged (159.9 ± 16.4 nm) in animals receiving anti-β3 F(ab)2. Podocyte foot process width was greater in control, F(ab)2-treated, animals (502 ± 34 nm) compared with animals treated with the anti-β3 F(ab)2 (357 ± 47 nm, P < .05). Renal β3 tyrosine phosphorylation decreased from 13 934 ± 6437 to 6730 ± 1524 (P < .01) scanning units in the anti-β3-treated group. We conclude that administration of an antibody that inhibits activation of the β3-subunit of αVβ3 that is induced by hyperglycemia attenuates proteinuria and early histologic changes of diabetic nephropathy, suggesting that it may have utility in preventing the progression of this disease complication.
Authors:
Laura A Maile; Walker H Busby; Katherine A Gollahon; William Flowers; Nikol Garbacik; Stefani Garbacik; Kara Stewart; Timothy Nichols; Dwight Bellinger; Amit Patel; Paul Dunbar; Matt Medlin; David Clemmons
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Publication Detail:
Type:  Journal Article     Date:  2014-08-29
Journal Detail:
Title:  Endocrinology     Volume:  155     ISSN:  1945-7170     ISO Abbreviation:  Endocrinology     Publication Date:  2014 Dec 
Date Detail:
Created Date:  2014-11-22     Completed Date:  -     Revised Date:  2014-12-09    
Medline Journal Info:
Nlm Unique ID:  0375040     Medline TA:  Endocrinology     Country:  United States    
Other Details:
Languages:  eng     Pagination:  4665-75     Citation Subset:  AIM; IM    
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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