Inhibition of v5 Integrin Attenuates Vascular Permeability and Protects against Renal Ischemia-Reperfusion Injury.

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 v5 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 v5 in a rat model of renal IRI. Pretreatment with this anti-v5 antibody significantly reduced serum creatinine levels, diminished renal damage detected by histopathologic evaluation, and decreased levels of injury biomarkers. Notably, therapeutic treatment with the v5 antibody 8 hours after IRI also provided protection from injury. Global gene expression profiling of post-ischemic kidneys showed that v5 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 v5 antibody treatment. Immunostaining for v5 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 v5 in modulating vascular leak. Additional studies showed v5 functions in the adhesion and migration of kidney pericytes Initial studies monitoring renal blood flow after IRI did not find significant effects with v5 inhibition; however, future studies should explore the contribution of vasomotor effects. These studies identify a role for v5 in modulating injury-induced renal vascular leak, possibly through effects on pericyte adhesion and migration, and reveal v5 inhibition as a promising therapeutic strategy for AKI.