IL-1B can serve as a healing process and is a critical regulator of diabetic foot ulcer

Abstract

Background: Diabetic foot ulcer (DFU) is the main cause of disability in diabetic patients. However, the molecular changes underlying the occurrence and progression of DFU remain unclear. We conducted this study to examine gene alterations in different DFU patients.Methods: GSE143735 and GSE134431 transcriptome data sets were acquired from the Gene Expression Omnibus database, and differential expression analyses of the genes in these data sets were performed.A functional enrichment analysis of the differentially expressed genes (DEGs) was performed using clusterProfiler package in R. To examine the correlations between DEGs and significant immune-related genes, we identified the intersecting ulcer-related DEGs, healing-related DEGs, and immune-related DEGs.Finally, we further investigate the relationship between the selected genes with immune cell regulation via a single-sample gene set enrichment analysis, and the infiltration of 28 immune cells in common diabetes samples, unhealed DFU samples, and healed samples DFU were compared.Results: We found 238 upregulated genes and 207 downregulated genes in the diabetic foot (DF) patients with ulcers compared to the DF patients without ulcers, and 74 upregulated genes and 28 downregulated genes in the healed samples compared to the unhealed samples. To examine the main biological functions, we conducted a functional enrichment analysis. The results showed that the biological functions of functional enrichment analysis included neutrophil degranulation, leukocyte chemotaxis, myeloid leukocyte migration, phagosome, cytokine-cytokine receptor interaction, and the chemokine signaling pathway. Interleukin (IL)-1B was more highly expressed in patients with ulcers and healed DFU patients than those without ulcers and unhealed DFU patients. Finally, the immune cell abundance difference results showed that activated cluster of differentiation (CD) 8 T cells, central memory CD8 T cells, T follicular helper cells, myeloid-derived suppressor cells, natural killer T cells and monocytes were more highly infiltrated in normal diabetes patients and healed DFU patients than unhealed DFU patients. However, no difference was found between DF patients with and without ulcers.Conclusions: IL-1B is an inflammation gene that can be used to assess and regulate DFU progression.

Advancements in non‐invasive skin sampling: Clinical conditions characterization via the assessment of skin surface cytokine biomarkers

“…IL-1β is associated with impaired wound healing. 34,35 Thus, it is not surprising that IL-1β was found to be higher in lesional diabetic areas compared to the control in this study (Figure 4A).…”

Healing mechanism of diabetic foot ulcers using single-cell RNA-sequencing

“…In addition to paying attention to the treatment of systemic factors, such as the control of blood sugar, blood pressure, blood lipid, anti-infection and the improvement of microcirculation, we must also pay attention to the standardized treatment of chronic wound itself. Only the comprehensive coordinated treatment of whole body and local can promote the healing of chronic difficult wound ( 22 , 23 ). DFU healing is a multi-step process that requires the coordination of 4 distinct but overlapping physiologically logical phases, including hemostasis, inflammation, proliferation, and remodeling ( 24 ).…”

Metabolism‐related biomarkers, molecular classification, and immune infiltration in diabetic ulcers with validation

“…For instance, targeting specific aspects of intratumor metabolisms, like the hexosamine biosynthesis pathway or glutamine metabolism, can boost the immune response and make tumors sensitive to checkpoint blockade 10 . Likewise, in DU wounds, the immune infiltrating microenvironment sustains a persistent inflammatory response 11 . It has been proven that the transition of M1 to M2 macrophages appears impaired in diabetic wounds 12 .…”

“…10 Likewise, in DU wounds, the immune infiltrating microenvironment sustains a persistent inflammatory response. 11 It has been proven that the transition of M1 to M2 macrophages appears impaired in diabetic wounds. 12 Immunological research at DUs has led to many immunotherapies.…”