Emerging genes as therapeutic targets for gene therapy in diabetic foot ulcers (DFUs).
| Target | Model | Strategy/approach | Outcome |
|---|---|---|---|
| PGI1 (integron class 1 gene)[120] | 50 specimens from DFU patients | Sample analysis revealed significantly increased integron class 1 gene in Proteus mirabilis isolated from diabetic foot infections. | The analysis of 50 DFU specimens showed a high prevalence of class 1 integrons among patients with P. mirabilis isolates.The PGI1 pathway may have therapeutic significance. |
| CXCR4 [110]CXCR4 [121] | GEO database analysis (DFU patient data) | The study identified differentially expressed genes and performed enrichment analysis to reveal the related biological pathways. | GEO database analysis revealed an important role of CXCR4 and its related pathways in the pathogenesis of DFUs [110]. CXCR4 also emerges as a potential target for intervention, along with PGI2, CSF3R, and CSF2RA, in clinical trials analysis of DFU [121].CXCR4 may be a potential target in DFU management. |
| Hippo-YAP signaling pathway [122] | Single-cell RNA sequencing of tissues from a diabetic mouse model | Mouse models were used to induce ulcers, and tissues were characterized histologically. Sequencing analysis was conducted to investigate the role of the TFAP2A-LIFR-Hippo-YAP signaling axis in regulating macrophage M2 polarization and its critical function in DFU wound healing. | Bulk and single-cell RNA sequencing of diabetic wounds revealed the critical role of macrophage M2 polarization mediated by TFAP2A, a central regulatory gene in macrophage function, in DFU healing.TFAP2A-LIFR-Hippo-YAP signaling axis accelerates DFU wound healing through the induction of macrophage M2 polarization.The immunoregulatory role of TFAP2A in DFU makes it a promising therapeutic target. |
| YAP-TAZ signaling [123] | Tissues from the ear wounds of diabetic mice | Gene and protein expression analyses on control and diabetic tissues.The aim was to evaluate the cellular regulation of Hippo and related pathway targets after plasma treatment. | The analysis of ear wounds in diabetic mice treated with cold plasma showed that cold plasma accelerated healing by increasing re-epithelialization and modifying extracellular matrix components involving YAP-TAZ signaling.YAP-TAZ signaling and activated TGF-β-regulated cellular regulation after gas plasma treatment have therapeutic potential, and YAP-TAZ is an attractive target. |
| SCUBE1 and RNF103-CHMP3 [124] | GEO database analysis of 15 DFU human samples | Differential gene analysis.Enrichment analysis.Protein-protein interaction network analysis. | SCUBE1 and RNF103-CHMP3, identified as key genes significantly associated with DFU, may be potential biomarkers and therapeutic targets. |
CXCR4: C-X-C motif chemokine receptor 4; GEO: Gene Ontology; Hippo-YAP: Hippo-associated factors, the yes-associated protein; LIFR: leukemia inhibitory factor receptor; TFAP2A: transcription factor AP-2 alpha; TGF: transforming growth factor; YAP-TAZ: yes-associated protein-transcriptional co-activator with PDZ binding motif.
IFA: Writing—original draft. VAG: Writing—original draft. VR: Conceptualization, Writing—original draft, Writing—review & editing. All authors read and approved the submitted version.
The authors declare that they have no conflicts of interest.
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The authors received no specific funding for this study.
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