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Analysis of Combinatorial miRNA Treatments to Regulate Cell Cycle and Angiogenesis
Published on: March 30, 2019
Nr-CWS regulates METTL3-mediated m6A modification of CDS2 mRNA in vascular endothelial cells and has prognostic
Jingyu Zhang1,2, Feifei Chen2,3, Wuhan Wei1,2
1Department of Plastic Surgery, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China.
Abstract:
Metabolic memory (MM) is a major factor in the delayed wound healing observed in diabetic patients. While "Nocardia rubrum cell wall skeleton" (Nr-CWS) is utilized to enhance macrophage proliferation in immune diseases, its impact on MM wounds in diabetes is unclear. This study demonstrates that transient hyperglycemia leads to prolonged damage in vascular endothelial cells by decreasing METTL3 expression, leading to decreased RNA methylation and impaired cellular metabolism. Remarkably, Nr-CWS application increases METTL3 levels in these cells, facilitating the recovery of cell function. Further in vivo and in vitro analyses demonstrate that transient hyperglycemia-induced reduction in METTL3 hinders RNA methylation of the downstream gene Cds2, impacting mitochondrial function and energy metabolism and consequently reducing angiogenic capacity in endothelial cells. This impairment significantly influences diabetic wound healing. Our findings highlight the profound impact of transient hyperglycemia on wound healing, establishing METTL3 as a significant role in vascular complications of diabetes. This study not only elucidates the pathophysiological mechanisms behind MM in diabetic wounds but also suggests Nr-CWS as a potential therapeutic agent, offering a novel approach for treating diabetic wounds.
Insights
Transient hyperglycemia impairs diabetic wound healing by reducing METTL3, affecting RNA methylation and cell metabolism. Nocardia rubrum cell wall skeleton (Nr-CWS) shows potential therapeutic benefits by restoring METTL3 levels.
Area of Science:
- Molecular Biology
- Endocrinology
- Wound Healing Research
Background:
- Metabolic memory (MM) significantly delays wound healing in diabetic patients.
- Nocardia rubrum cell wall skeleton (Nr-CWS) is known to enhance macrophage proliferation but its role in diabetic MM wounds is unexplored.
- Transient hyperglycemia causes lasting damage to vascular endothelial cells.
Purpose of the Study:
- To investigate the impact of transient hyperglycemia on vascular endothelial cells and diabetic wound healing.
- To elucidate the role of METTL3 in metabolic memory-associated wound complications.
- To evaluate the therapeutic potential of Nr-CWS in diabetic wound healing.
Main Methods:
- In vivo and in vitro analyses of vascular endothelial cells.
- Assessment of METTL3 expression and RNA methylation levels.
- Evaluation of Cds2 gene expression, mitochondrial function, and angiogenic capacity.
Main Results:
- Transient hyperglycemia decreases METTL3 expression, impairing RNA methylation and cellular metabolism in endothelial cells.
- Nr-CWS application increases METTL3 levels, aiding endothelial cell function recovery.
- Reduced METTL3 hinders Cds2 RNA methylation, impacting mitochondrial function, energy metabolism, and angiogenesis, thus worsening diabetic wound healing.
Conclusions:
- Transient hyperglycemia has a profound negative impact on diabetic wound healing via METTL3 downregulation.
- METTL3 plays a critical role in the vascular complications associated with diabetes.
- Nr-CWS presents a promising therapeutic strategy for treating diabetic wounds by restoring METTL3 levels.
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