| First Author | You H | Year | 2013 |
| Journal | Kidney Int | Volume | 84 |
| Issue | 6 | Pages | 1189-97 |
| PubMed ID | 23760286 | Mgi Jnum | J:318973 |
| Mgi Id | MGI:6862150 | Doi | 10.1038/ki.2013.215 |
| Citation | You H, et al. (2013) Arginase inhibition mediates renal tissue protection in diabetic nephropathy by a nitric oxide synthase 3-dependent mechanism. Kidney Int 84(6):1189-97 |
| abstractText | Recently, we showed that pharmacological blockade or genetic deficiency of arginase-2 confers kidney protection in diabetic mouse models. Here, we tested whether the protective effect of arginase inhibition is nitric oxide synthase 3 (eNOS) dependent in diabetic nephropathy. Experiments were conducted in eNOS-knockout and their wild-type littermate mice using multiple low doses of vehicle or streptozotocin, and treated with continuous subcutaneous infusion of vehicle or the arginase inhibitor S-(2-boronoethyl)-L-cysteine by an osmotic pump. Inhibition of arginases for 6 weeks in diabetic wild-type mice significantly attenuated albuminuria, the increase in plasma creatinine and blood urea nitrogen, histopathological changes, kidney fibronectin and TNF-alpha expression, kidney macrophage recruitment, and oxidative stress compared with vehicle-treated diabetic wild-type mice. Arginase inhibition in diabetic eNOS-knockout mice failed to affect any of these parameters, but reduced kidney macrophage recruitment and kidney TNF-alpha expression compared with vehicle-treated diabetic eNOS-knockout mice. Furthermore, diabetic wild-type and eNOS-knockout mice exhibited increased kidney arginase-2 protein, arginase activity, and ornithine levels. Thus, arginase inhibition mediates renal tissue protection in diabetic nephropathy by an eNOS-dependent mechanism and has an eNOS-independent effect on kidney macrophage recruitment. |
