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Deprecated: Implicit conversion from float 265.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Endocrinology 2014 ; 155 (12): 4665-75 Nephropedia Template TP
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Blocking Ligand Occupancy of the ?V?3 Integrin Inhibits the Development of Nephropathy in Diabetic Pigs #MMPMID25171599
Maile LA; Busby WH; Gollahon KA; Flowers W; Garbacik N; Garbacik S; Stewart K; Nichols T; Bellinger D; Patel A; Dunbar P; Medlin M; Clemmons D
Endocrinology 2014[Dec]; 155 (12): 4665-75 PMID25171599show ga
Hyperglycemia stimulates secretion of ?V?3 ligands from vascular cells, including endothelial cells, resulting in activation of the ?V?3 integrin. This study determined whether blocking ligand occupancy of ?V?3 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 ?3-subunit, and 10 received a control IgG F(ab)2 for 18 weeks. Nondiabetic pigs excreted 115 ± 50 ?g of protein/mg creatinine compared with control F(ab)2-treated diabetic animals (218 ± 57 ?g/mg), whereas diabetic animals treated with the anti-?3 F(ab)2 excreted 119 ± 55 ?g/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-?3 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-?3 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-?3 F(ab)2 (357 ± 47 nm, P < .05). Renal ?3 tyrosine phosphorylation decreased from 13 934 ± 6437 to 6730 ± 1524 (P < .01) scanning units in the anti-?3-treated group. We conclude that administration of an antibody that inhibits activation of the ?3-subunit of ?V?3 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.