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Receptor for advanced glycation end as drug targets in diabetes-induced skin lesion

Xiang-Fang Chen1, Wei Tang1, Wei-Dong Lin2

  • 1Department of Endocrinology, Changzheng Hospital, Second Military Medical University Shanghai 200003, China.

American Journal of Translational Research
|March 25, 2017
PubMed

Insights

Metformin protects skin cells from diabetes damage by inhibiting the receptor for advanced glycation end (RAGE). This study shows Metformin rectifies RAGE overexpression, reducing cell cycle arrest, apoptosis, and inflammation in diabetic conditions.

Area of Science:

  • Biochemistry
  • Dermatology
  • Pharmacology

Background:

  • The receptor for advanced glycation end (RAGE) is implicated in various diseases.
  • The impact of diabetic medications on RAGE-mediated skin lesions in long-term diabetes is not well understood.

Purpose of the Study:

  • To investigate the effects of metformin on RAGE-induced skin lesions in diabetic conditions.
  • To elucidate the protective mechanisms of metformin against RAGE overexpression in diabetic rats and human keratinocytes (HaCaT cells).

Main Methods:

  • Assessed RAGE expression in diabetic rat models and HaCaT cells.
  • Evaluated the impact of metformin on cell cycle arrest, apoptosis, and protein levels.
  • Measured the secretion of inflammatory factors (TNF-α, IL-1β, IL-6, ICAM-1, COX-2) in HaCaT cells.
  • Analyzed the activation of p38 and NF-κB signaling pathways.

Main Results:

  • RAGE was overexpressed in diabetic rats and HaCaT cells.
  • Metformin treatment rectified RAGE overexpression-induced cell cycle arrest, apoptosis, and altered protein levels.
  • Metformin corrected the secretion of inflammatory factors induced by RAGE overexpression.
  • Metformin significantly reduced RAGE overexpression-induced p38 and NF-κB activation.

Conclusions:

  • Metformin protects HaCaT cells against diabetes-induced injuries and inflammatory responses.
  • The protective effect of metformin is mediated through the inhibition of activated RAGE.
  • This study provides novel insights into the therapeutic potential of metformin in managing RAGE-related complications in diabetes.
Keywords:
DiabetesRAGEapoptosisdrug targetinflammatory response

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