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The RAGE/DIAPH1 Signaling Axis & Implications for the Pathogenesis of Diabetic Complications

Ravichandran Ramasamy1, Alexander Shekhtman2, Ann Marie Schmidt1

  • 1Diabetes Research Program, Department of Medicine, New York University Grossman School of Medicine, New York, NY 10016, USA.

International Journal of Molecular Sciences
|May 14, 2022
PubMed

Insights

The RAGE/DIAPH1 pathway contributes to diabetic complications by promoting inflammation via interferon signaling. Targeting intracellular RAGE signaling offers a promising therapeutic strategy for managing diabetes.

Area of Science:

  • Molecular Biology
  • Immunology
  • Endocrinology

Background:

  • The receptor for advanced glycation end products (RAGE) and Diaphanous 1 (DIAPH1) signaling axis is increasingly implicated in the pathogenesis of diabetic complications.
  • Hyperglycemia in type 1 and type 2 diabetes leads to maladaptive effects mediated by RAGE ligand-receptor interactions.

Purpose of the Study:

  • To review recent advances in understanding the pathobiology of the RAGE/DIAPH1 axis in diabetic complications.
  • To highlight emerging therapeutic strategies targeting RAGE intracellular signaling.

Main Methods:

  • Literature review of recent studies on RAGE and DIAPH1 in diabetes.
  • Analysis of the role of RAGE ligands as damage-associated molecular patterns (DAMPs).
  • Examination of RAGE's impact on interferon signaling pathways, including IRF7 upregulation.

Main Results:

  • RAGE ligands acting as DAMPs can upregulate interferon regulatory factor 7 (IRF7), leading to pro-inflammatory effects.
  • The RAGE/DIAPH1 axis plays a significant role in the cellular and tissue dysfunction associated with diabetes.
  • Previous clinical targeting of RAGE has shown limited success.

Conclusions:

  • Targeting intracellular RAGE signaling pathways presents a promising therapeutic avenue for diabetic complications.
  • Further research into the RAGE/DIAPH1 axis and its inflammatory signaling is crucial for developing effective treatments.
  • Understanding the interplay between RAGE, DAMPs, and interferon signaling is key to addressing diabetic complications.
Keywords:
DIAPH1RAGEdiabetesdiabetic accelerated atherosclerosisdiabetic complicationsdiabetic kidney diseaseinterferon pathwaysmall molecule antagonist

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