Role of endothelial nitric oxide synthase in diabetic nephropathy: lessons from
diabetic eNOS knockout mice.
Authors Takahashi T, Harris RC
Submitted By Takamune Takahashi on 1/5/2015
Status Published
Journal Journal of diabetes research
Year 2014
Date Published
Volume : Pages 2014 : 590541
PubMed Reference 25371905
Abstract Diabetic nephropathy (DN) is the leading cause of end-stage renal disease in
many countries. The animal models that recapitulate human DN undoubtedly
facilitate our understanding of this disease and promote the development of new
diagnostic markers and therapeutic interventions. Based on the clinical evidence
showing the association of eNOS dysfunction with advanced DN, we and others have
created diabetic mice that lack eNOS expression and shown that eNOS-deficient
diabetic mice exhibit advanced nephropathic changes with distinct features of
progressive DN, including pronounced albuminuria, nodular glomerulosclerosis,
mesangiolysis, and arteriolar hyalinosis. These studies clearly defined a
critical role of eNOS in DN and developed a robust animal model of this disease,
which enables us to study the pathogenic mechanisms of progressive DN. Further,
recent studies with this animal model have explored the novel mechanisms by
which eNOS deficiency causes advanced DN and provided many new insights into the
pathogenesis of DN. Therefore, here we summarize the findings obtained with this
animal model and discuss the roles of eNOS in DN, unresolved issues, and future
investigations of this animal model study.

Investigators with authorship
Raymond HarrisVanderbilt University
Takamune TakahashiVanderbilt University