Pattern recognition receptor-mediated inflammation in diabetic vascular complications

Med Res Rev. 2020 Nov;40(6):2466-2484. doi: 10.1002/med.21711. Epub 2020 Jul 10.

Abstract

The innate immune system contains multiple classes of pattern recognition receptors (PRRs), which recognize pathogen-associated molecular patterns (PAMPs) and danger-associated molecular patterns (DAMPs) in the intracellular and extracellular space. Although PRRs are indispensable for the detection and clearance of invading pathogens, dysregulated PRR activation by extrinsic and intrinsic factors leads to inflammatory diseases. PRR-mediated inflammation has been shown to play a pivotal role in the pathogenesis of diabetic vascular complications (DVCs), which are the leading causes of morbidity and mortality in diabetic patients. Upon sensing hyperglycemia-generated DAMPs, PRRs activate intracellular signaling pathways leading to the production of proinflammatory cytokines and chemokines in various cells of the kidney, brain, eye, and heart. The resulting chronic, low-grade inflammation contributes to DVCs. In this review, we summarize the role of PRRs in DVCs including diabetic nephropathy, neuropathy, retinopathy, and cardiomyopathy. We propose that targeting PRRs and associated signaling pathways may be beneficial for the management of DVCs.

Keywords: diabetic vascular complication; drug development; inflammation; pattern recognition receptor; signaling pathway.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Diabetes Mellitus*
  • Diabetic Angiopathies*
  • Humans
  • Immune System
  • Inflammation
  • Receptors, Pattern Recognition
  • Signal Transduction

Substances

  • Receptors, Pattern Recognition