Microinflammation in the pathogenesis of diabetic nephropathy.
Diabetic nephropathy is the leading cause of end-stage renal failure in developed countries. Furthermore, diabetic nephropathy is related to the risk of cardiovascular diseases and an increase in mortality of diabetic patients. Several factors are involved in the development of nephropathy, including glomerular hyperfiltration, oxidative stress, accumulation of advanced glycation end-products, activation of protein kinase C, acceleration of the polyol pathway and over-expression of transforming growth factor-β. Recently, accumulated data have emphasized the critical roles of chronic low-grade inflammation, 'microinflammation', in the pathogenesis of diabetic nephropathy, suggesting that microinflammation is a common mechanism in the development of diabetic vascular complications. Expression of cell adhesion molecules, chemokines and pro-inflammatory cytokines are increased in the renal tissues of diabetic patients and animals. Deficiency of pro-inflammatory molecules results in amelioration of renal injuries after induction of diabetes in mice. Plasma and urinary levels of cytokines, chemokines and cell adhesion molecules, are elevated and correlated with albuminuria. Several kinds of drugs that have anti-inflammatory actions as their pleiotropic effects showed renoprotective effects on diabetic animals. Modulation of the inflammatory process prevents renal insufficiency in diabetic animal models, suggesting that microinflammation is one of the promising therapeutic targets for diabetic nephropathy, as well as for cardiovascular diseases.
Center for Innovative Clinical Medicine Okayama University Hospital Okayama Japan ; Department of Medicine and Clinical Science Okayama University Graduate School of Medicine Dentistry, and Pharmaceutical Science Okayama Japan.
Kenichi
K
Shikata
Center for Innovative Clinical Medicine Okayama University Hospital Okayama Japan ; Department of Medicine and Clinical Science Okayama University Graduate School of Medicine Dentistry, and Pharmaceutical Science Okayama Japan.
Hirofumi
H
Makino
Diabetic nephropathy; Inflammation; Microinflammation