Toll-like Receptors: Sensing and Reacting to Diabetic Injury in the Kidney

Abstract

Diabetes mellitus (DM) is a chronic endocrine disease distinguished by hyperglycemia due to disturbance in carbohydrate or lipid metabolism or insulin function. To date, diabetes, and its complications, is established as a global cause of morbidity and mortality. The intended aim during the management of diabetes is to maintain blood glucose close to normal because the majority of patients have poor control of their elevated blood glucose and are highly prone to severe macrovascular and microvascular complications. To decrease the burden of the disease and its complications, scientists from various disciplines are working intensively to identify novel and promising drug targets for diabetes and its complications. Innate immunity plays a crucial role in the pathogenesis of type 2 diabetes andrelated complications. Since the toll-like receptors (TLRs) are central to innateimmunity, it appears that they are important participants in the development andpathogenesis of the disease. Previous investigations demonstrated that TLR2 homodimers and TLR2 heterodimers with TLR1 or TLR6 activate innate immunityupon recognition of damage-associated molecular patterns (DAMPs). Accumulating evidence indicates that immunologic and inflammatoryelements play an important role in initiating and orchestratingthe development of diabetic nephropathy (DN), but untilrecently, the identity of specific innate immune pattern recognitionreceptors or sensors that recognize diverse diabetic‘danger signals’ to trigger the proinflammatory cascade duringDN remains unknown. Toll-like receptors (TLRs) are an emergingfamily of receptors that recognize pathogen-associated molecularpatterns as well as damage-associated molecular patternsto promote the activation of leukocytes and intrinsic renal cellsin non-immune kidney disease. Recent data from in vitro and invivo studies have highlighted the critical role of TLRs, mainlyTLR2 and TLR4, in the pathogenesis of DN.