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Inhibition of αvß5 Integrin Attenuates Vascular Permeability and Protects against Renal Ischemia-Reperfusion Injury.
McCurley, Amy; Alimperti, Stella; Campos-Bilderback, Silvia B; Sandoval, Ruben M; Calvino, Jenna E; Reynolds, Taylor L; Quigley, Catherine; Mugford, Joshua W; Polacheck, William J; Gomez, Ivan G; Dovey, Jennifer; Marsh, Graham; Huang, Angela; Qian, Fang; Weinreb, Paul H; Dolinski, Brian M; Moore, Shaun; Duffield, Jeremy S; Chen, Christopher S; Molitoris, Bruce A; Violette, Shelia M; Crackower, Michael A.
Afiliación
  • McCurley A; Biogen Inc., Cambridge, Massachusetts; amy.mccurley@biogen.com.
  • Alimperti S; Department of Biomedical Engineering, Boston University, Boston, Massachusetts.
  • Campos-Bilderback SB; The Wyss Institute for Biologically Inspired Engineering at Harvard University, Boston, Massachusetts.
  • Sandoval RM; Indiana University School of Medicine, The Roudebush Veterans Affair Medical Center, Indiana Center for Biological Microscopy, Indianapolis, Indiana; and.
  • Calvino JE; Indiana University School of Medicine, The Roudebush Veterans Affair Medical Center, Indiana Center for Biological Microscopy, Indianapolis, Indiana; and.
  • Reynolds TL; Biogen Inc., Cambridge, Massachusetts.
  • Quigley C; Biogen Inc., Cambridge, Massachusetts.
  • Mugford JW; Biogen Inc., Cambridge, Massachusetts.
  • Polacheck WJ; Biogen Inc., Cambridge, Massachusetts.
  • Gomez IG; Department of Biomedical Engineering, Boston University, Boston, Massachusetts.
  • Dovey J; The Wyss Institute for Biologically Inspired Engineering at Harvard University, Boston, Massachusetts.
  • Marsh G; Biogen Inc., Cambridge, Massachusetts.
  • Huang A; Biogen Inc., Cambridge, Massachusetts.
  • Qian F; Biogen Inc., Cambridge, Massachusetts.
  • Weinreb PH; Biogen Inc., Cambridge, Massachusetts.
  • Dolinski BM; Biogen Inc., Cambridge, Massachusetts.
  • Moore S; Biogen Inc., Cambridge, Massachusetts.
  • Duffield JS; Biogen Inc., Cambridge, Massachusetts.
  • Chen CS; Biogen Inc., Cambridge, Massachusetts.
  • Molitoris BA; Biogen Inc., Cambridge, Massachusetts.
  • Violette SM; Department of Biomedical Engineering, Boston University, Boston, Massachusetts.
  • Crackower MA; The Wyss Institute for Biologically Inspired Engineering at Harvard University, Boston, Massachusetts.
J Am Soc Nephrol ; 28(6): 1741-1752, 2017 Jun.
Article en En | MEDLINE | ID: mdl-28062569
Ischemia-reperfusion injury (IRI) is a leading cause of AKI. This common clinical complication lacks effective therapies and can lead to the development of CKD. The αvß5 integrin may have an important role in acute injury, including septic shock and acute lung injury. To examine its function in AKI, we utilized a specific function-blocking antibody to inhibit αvß5 in a rat model of renal IRI. Pretreatment with this anti-αvß5 antibody significantly reduced serum creatinine levels, diminished renal damage detected by histopathologic evaluation, and decreased levels of injury biomarkers. Notably, therapeutic treatment with the αvß5 antibody 8 hours after IRI also provided protection from injury. Global gene expression profiling of post-ischemic kidneys showed that αvß5 inhibition affected established injury markers and induced pathway alterations previously shown to be protective. Intravital imaging of post-ischemic kidneys revealed reduced vascular leak with αvß5 antibody treatment. Immunostaining for αvß5 in the kidney detected evident expression in perivascular cells, with negligible expression in the endothelium. Studies in a three-dimensional microfluidics system identified a pericyte-dependent role for αvß5 in modulating vascular leak. Additional studies showed αvß5 functions in the adhesion and migration of kidney pericytes in vitro Initial studies monitoring renal blood flow after IRI did not find significant effects with αvß5 inhibition; however, future studies should explore the contribution of vasomotor effects. These studies identify a role for αvß5 in modulating injury-induced renal vascular leak, possibly through effects on pericyte adhesion and migration, and reveal αvß5 inhibition as a promising therapeutic strategy for AKI.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Permeabilidad Capilar / Daño por Reperfusión / Receptores de Vitronectina / Riñón Límite: Animals Idioma: En Revista: J Am Soc Nephrol Asunto de la revista: NEFROLOGIA Año: 2017 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Permeabilidad Capilar / Daño por Reperfusión / Receptores de Vitronectina / Riñón Límite: Animals Idioma: En Revista: J Am Soc Nephrol Asunto de la revista: NEFROLOGIA Año: 2017 Tipo del documento: Article Pais de publicación: Estados Unidos