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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.
Abstract:
Delayed repair is a serious public health concern for diabetic populations. Intercellular adhesion molecule 1 (ICAM-1) and Lymphocyte function-associated antigen 1 (LFA-1) play important roles in orchestrating the repair process. However, little is known about their effects on endothelial cell (EC) proliferation and neutrophil activity in subjects with hyperglycemia (HG). We cultured ECs and performed a scratch-closure assay to determine the relationship between ICAM-1 and EC proliferation. Specific internally labeled bacteria were used to clarify the effects of ICAM-1 and LFA-1 on neutrophil phagocytosis. Transwell assay and fluorescence-activated cell sorting analysis evaluated the roles of ICAM-1 and LFA-1 in neutrophil recruitment. ICAM-1+/+ and ICAM-1-/- mice were used to confirm the findings in vivo. The results demonstrated that HG decreased the expression of ICAM-1, which lead to the low proliferation of ECs. HG also attenuated neutrophil recruitment and phagocytosis by reducing the expression of ICAM-1 and LFA-1, which were strongly associated with the delayed repair.
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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