Implication of the MAPK Signalling Pathway in the Pathogenesis of Diabetic Nephropathy

Abstract

Diabetes has become an emerging public health problem because of its serious complications, and high mortality and morbidity rates. Among the most common microvascular complications of diabetes is diabetic nephropathy (DN), which is a major cause of development of end-stage renal disease worldwide. The aetiopathogenesis of DN is not completely elucidated; however, studies have shown that the components of the MAPK signalling pathway play an essential role in the development and progression of the disease. The MAPK family is mainly composed of three subgroups: extracellular signal-regulated kinases 1 and 2, c-Jun N-terminal kinases (JNK) 1–3, and p38 MAPK, all of which are related to several cellular functions, such as cell death, differentiation, proliferation, motility, survival, stress response, and cell growth. In diabetic kidney disease, the MAPK pathway can be activated by processes resulting from hyperglycaemia (polyol pathway products, oxidative stress, and accumulation of advanced glycosylation end-products) and by angiotensin II, and it is related to several renal pathological processes. This review aims to summarise the role of the MAPK signalling pathway in diabetic nephropathy, as well as to link the biological aspects that contribute to clarify the pathological process behind the disease.