For citation purposes: Fujita T. Extra-immunological role of complement activation in diabetic nephropathy. OA Nephrology 2013 Oct 25;1(2):19.

Critical review


Extra-immunological role of complement activation in diabetic nephropathy

T Fujita

Authors affiliations

Department of Nephrology, Hypertension and Endocrinology, Nihon University School of Medicine, Tokyo, Japan

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Activation of complement cascades has been implicated in the crosstalk between the immune system and metabolism. Membrane attack complex, which is formed by activation of the complement system, plays a role in the formation of atherosclerotic plaque. Acylation stimulating protein, a C3 breakdown product (C3a desArg), is associated with insulin resistance and is implicated in tissue inflammation. Obesity and dyslipidemia-induced ASP-C5L2 (C5a receptor-like 2) axis stimulation induce diabetic microvascular endothelial dysfunction. Moreover, intracellular reactive oxygen species in the microvascular endothelium and the coagulation system also induce complement activation, resulting in acceleration of atherosclerosis and tissue injury in the kidney. A substantial amount of evidence has elucidated the association between complement activation and the progression of kidney injury. These insights into the pathological mechanisms associated with several complement pathways will aid in the development of novel therapeutic approaches. The aim of this review was to discuss the extra immunological role of complement activation in diabetic nephropathy.


The complement system is a versatile player not only in host defence but also in complex metabolic and regenerative functions. Further studies are warranted to identify in more detail components of the complement system as possible targets for prevention of diabetic nephropathy.

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