Pathophysiological role and therapeutic implications of inflammation in diabetic nephropathy

Table 1 Mechanisms and consequences related to protein kinase C activation-mediated harmful effects in diabetes mellitus

Reduction of nitric oxide production

Increased endothelin-1, prostaglandin E2 and thromboxane A2

Induction of growth factor expression: Transforming growth factor-β and vascular endothelial growth factor

Accumulation of microvascular matrix, fibronectin and type IV collagen

Overexpression of fibrinolytic inhibitor plasminogen activator inhibitor-1

Activation of the transcription factor nuclear factor kappa B

Increased nicotinamide adenine dinucleotide phosphate oxidase activity

Blood-flow abnormalities

Alteration of vascular permeability

Induction of angiogenesis

Organ fibrosis

Capillary occlusion

Induction of inflammatory mediators

Stimulation of oxidative stress

Table 2 Inflammatory cytokine-related effects potentially involved in the development and progression of renal injury in diabetes

Increase expression and synthesis of chemokines, adhesion molecules, transcription factors, cytokines, growth factors and mediators of inflammation

Alteration of synthesis of prostaglandins and hyaluronan

Stimulation of oxidative stress

Induction of intraglomerular hemodynamic abnormalities

Increase of vascular endothelial cell permeability

Induction of cell proliferation and contraction, and inhibition of endothelium relaxation

Increase fibronectin expression

Induction of cell apoptosis and necrosis

Induction of glomerular hypertrophy

Stimulation of plasminogen activator inhibitor-1 production

Reduction of tissue factor inhibitor and thrombomodulin expression

Stimulation of inflammatory cells recruitment and activation

Induction of major histocompatibility complex antigen expression