TABLE 1.
Pathogenesis of delayed wound healing of diabetic ulcers.
| Influencing factor | Target | Conventional role |
|---|---|---|
| Increased inflammatory cells and proinflammatory factors | Macrophage inflammatory protein factor | Expressed in the form of membrane binding on the surface of inflammatory cells, epithelial cells, macrophages, and vascular smooth muscle cells |
| Macrophage polarization | Caused by hyperglycemia and oxidative stress and be the major reason for delayed wound healing | |
| Insufficient oxygen supply to ulcer wound | Narrowing of blood vessels | Causes insufficient oxygen supply to the wound |
| Glycosylation of haemoglobin | Causes insufficient supply of nutrients and oxygen in the tissues, thereby delays the healing process | |
| Metamorphin skin tissue damage | Activated after injury and induces increased expression of pro-inflammatory chemokines and aggravates the cellular stress response by promoting the accumulation of unfolded proteins in the endoplasmic reticulum | |
| Ulcer wound ischemia | MiR-210 | Plays a crucial role in limiting the proliferation of keratinocytes and delays wound healing |
| MiR-200b | Derepresses the transcription factor endothelial transcription factor GATA2 and VEGFR2 to turn on wound angiogenesis | |
| MiR-21, miR-198, miR-130a, miR-26A, and miR-146 | Involved in re-epithelialization, delayed inflammatory response, fibroblast migration, keratinocyte migration and angiogenesis in the diabetic wounds | |
| Stromal cell proteins | Bind to a variety of proteins in ECM library and connect to homologous cell surface receptors | |
| Angiopoietin-like factor 4 (AL-4) | Delays the healing process by influencing angiogenesis and re-epithelialization | |
| Diabetic peripheral neuropathy | Abnormal glycosylation of neuronal proteins and abnormal activation of protein kinase C | Lead to neurological dysfunction and ischemia under conditions of hyperglycemia and oxidative stress |
| Growth factors | VEGF | Increases blood capillary density and improves blood perfusion and metabolism in injured tissues |
| IGF-1, IGF-2, TGF-β, PDGF, EGF, TNF-α, and IL-6 | Play a key role in initiating and maintaining different stages of wound healing | |
| Oxidative stress | NRF2 | Reduces apoptosis and promotes cell migration, proliferation and cell differentiability by regulating the adaptive response to oxidative stress |
| ATF-3 | Induces lymphatic B cell dysregulation and promote the occurrence of diabetic complications |