Hyperglycemia Decreases Epithelial Cell Proliferation and Attenuates Neutrophil Activity by Reducing ICAM-1 and LFA-1

Dongxu Qiu1, Lei Zhang1, Junkun Zhan2

  • 1Xiangya Hospital, Central South University, Changsha, China.

Frontiers in Genetics
|January 8, 2021
PubMed

Insights

Hyperglycemia impairs wound healing by reducing intercellular adhesion molecule 1 (ICAM-1) and lymphocyte function-associated antigen 1 (LFA-1). This affects endothelial cell proliferation and neutrophil activity, delaying repair in diabetic populations.

Area of Science:

  • Biomedical Science
  • Wound Healing Research
  • Diabetic Complications

Background:

  • Delayed wound repair is a significant public health issue in diabetic patients.
  • Intercellular adhesion molecule 1 (ICAM-1) and Lymphocyte function-associated antigen 1 (LFA-1) are crucial for tissue repair.
  • The impact of hyperglycemia on ICAM-1, LFA-1, endothelial cell proliferation, and neutrophil activity remains unclear.

Purpose of the Study:

  • To investigate the role of ICAM-1 and LFA-1 in endothelial cell proliferation and neutrophil function under hyperglycemic conditions.
  • To elucidate the mechanisms by which hyperglycemia affects wound repair.
  • To establish the association between ICAM-1, LFA-1 expression, and delayed repair in diabetes.

Main Methods:

  • Endothelial cells (ECs) were cultured and subjected to scratch-closure assays to assess proliferation.
  • Neutrophil phagocytosis was evaluated using internally labeled bacteria.
  • Transwell assays and fluorescence-activated cell sorting (FACS) were employed to analyze neutrophil recruitment.
  • Experiments were validated in vivo using ICAM-1 knockout and wild-type mice.

Main Results:

  • Hyperglycemia significantly decreased ICAM-1 expression, leading to reduced EC proliferation.
  • Hyperglycemia attenuated neutrophil recruitment and phagocytosis by downregulating ICAM-1 and LFA-1 expression.
  • Reduced expression of ICAM-1 and LFA-1 correlated strongly with delayed wound repair.

Conclusions:

  • Hyperglycemia negatively impacts key components of the wound healing process, including EC proliferation and neutrophil function.
  • The downregulation of ICAM-1 and LFA-1 under hyperglycemic conditions is a critical factor contributing to delayed repair in diabetic individuals.
  • Targeting ICAM-1 and LFA-1 pathways may offer therapeutic potential for improving wound healing in diabetic patients.

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