A breakthrough in diabetic nephropathy: the role of endothelial dysfunction.

Kanetsuna et al. [1] have published an important paper in the American Journal of Pathology, reporting that renal lesions resembling human diabetic nephropathy can be induced in mice made diabetic (with streptozotocin) which genetically lack endothelial nitric oxide synthase (eNOS). eNOS is a key enzyme in endothelial cells that produces nitric oxide (NO). In turn, NO has multiple functions in the vasculature, including acting as a vasodilator, anti-inflammatory, anti-thrombotic and anti-proliferative activities. In this study, diabetic eNOS knockout mice developed both renal functional (proteinuria, reduced glomerular filtration rate) and structural changes consistent with human diabetic nephropathy. Up to now, it has been difficult to develop in mice models of diabetic nephropathy that resemble human disease, so this article represents a breakthrough in the pathogenesis of diabetic nephropathy.