A Lower IL-34 Expression Is Associated With Non-Healing Diabetic Foot Ulcers

Abstract

Background: The non-healing of DFU is a major cause of high disability, morbidity, and mortality. Thus, new therapeutic targets and methods to help healing in patients with DFUs are major research hotspots.

Objective: This study examined the molecular differences between healing and non-healing DFUs to identify genes associated with diabetic foot ulcers (DFU) healing.

Methods: Differentially expressed genes (DEGs) were identified by bioinformatics. Samples were collected from patients with healing(n=10) and non-healing(n=10) DFUs from September 2021 to September 2022. IL-34 expression was measured by ELISA and qRT-PCT. The fibroblasts from healing and non-healing DFU were divided according to their gene signatures and subdivided based on their gene expression profile differences.

Results: A comparison of fibroblast subpopulation characteristics revealed that the proportion of subpopulation 4 was significantly higher in non-healing DFUs than in healing DFUs. Subpopulation 4 had 254 upregulated genes and 2402 downregulated genes in the non-healing compared with the healing DFUs. The DEGs were involved in several biological functions, including cytokine activity, receptor-ligand activity, signaling receptor activator activity, and receptor regulator activity. IL-34 was downregulated in non-healing compared with healing DFUs, suggesting a possible role of IL-34 in DFU healing. In the clinical specimens, IL-34 was significantly downregulated in non-healing DFUs, consistent with the bioinformatics results.

Conclusion: IL-34 expression is downregulated in non-healing DFU. IL-34 appears to be involved in DFU healing, but the exact causal relationship remains to be explored.

Keywords: Gene Expression Omnibus database; bioinformatics; diabetic foot ulcer; fibroblasts; healing; interleukin-34.