Universidad de Murcia. Departamento de Biología Celular e Histología
Abstract
Diabetic nephropathy (DN) is a major cause
of end-stage renal disease (ESRD), however, specific
treatment for DN has not yet been elucidated. Therefore,
it is critically important to understand the molecular
mechanism underlying DN to develop cause-related
therapeutic strategy. To date, various factors such as
hemodynamic changes and metabolic pathways have
been shown to be involved in the pathogenesis of DN.
Excessive glucose influx activates cellular signaling
pathways, including the diacylglycerol (DAG)-protein
kinase C (PKC) pathway, advanced glycation endproducts (AGE), polyol pathway, hexosamine pathway
and oxidative stress. These factors interact with one
another, thereby facilitating inflammatory processes,
leading to the development of glomerulosclerosis under
diabetic conditions. In addition to metabolic pathways,
Rho-kinase, an effector of small-GTPase binding protein
Rho, has been implicated as an important factor in the
pathogenesis of DN. A number of studies have
demonstrated that Rho-kinase plays key roles in the
development of DN by inducing endothelial dysfunction,
mesangial excessive extracellular matrix (ECM)
production, podocyte abnormality, and tubulointerstitial
fibrosis. In this review article, we describe our current
understanding of the signaling pathways in DN