Photobiomodulation at 660 nm Stimulates In Vitro Diabetic Wound Healing via the Ras/MAPK Pathway.

Diabetic foot ulcers (DFUs) are open chronic wounds that affect diabetic patients due to hyperglycaemia. DFUs are known for their poor response to treatment and frequently require amputation, which may result in premature death. The present study evaluated the effect of photobiomodulation (PBM) at 660 nm on wound healing via activation of Ras/MAPK signalling in diabetic wounded cells in vitro. This study used four human skin fibroblast cell (WS1) models, namely normal (N), wounded (W), diabetic (D), and diabetic wounded (DW). Cells were irradiated at 660 nm with 5 J/cm2. Non-irradiated cells (0 J/cm2) served as controls. Cells were incubated for 24 and 48 h post-irradiation, and the effect of PBM on cellular morphology and migration rate, viability, and proliferation was assessed. Basic fibroblast growth factor (bFGF), its phosphorylated (activated) receptor FGFR, and phosphorylated target proteins (Ras, MEK1/2 and MAPK) were determined by enzyme-linked immunosorbent assay (ELISA) and Western blotting; nuclear translocation of p-MAPK was determined by immunofluorescence. PBM resulted in an increase in bFGF and a subsequent increase in FGFR activation. There was also an increase in downstream proteins, p-Ras, p-MEK1/2 and p-MAPK. PBM at 660 nm led to increased viability, proliferation, and migration as a result of increased bFGF and subsequent activation of the Ras/MAPK signalling pathway. Therefore, this study can conclude that PBM at 660 nm stimulates in vitro diabetic wound healing via the bFGF-activated Ras/MAPK pathway.

The effect of photomodulation on fibroblast growth factor and the Ras/MAPK signalling pathway: a review.

OBJECTIVE: Current therapies and technologies used to treat hard-to-heal diabetic wounds are limited to a 50% healing rate. The rise in the percentage of lower limb non-traumatic amputations in patients with diabetes has caused an increased demand for alternative, effective and safe treatment modalities. Photobiomodulation therapy (PBMT) utilises light to induce physiological changes and provide therapeutic benefits and has been shown to increase the healing of hard-to-heal wounds through the release of growth factors. The aim of this narrative review is to investigate the effect of photobiomodulation (PBM) on fibroblast growth factor (FGF) and the role of the Ras/MAPK signalling pathway in diabetic wound healing. METHOD: Relevant journal articles were obtained through PubMed and Google Scholar. RESULTS: Experimental and clinical findings from the review show that PBM can stimulate the release of growth factors, including FGF, an essential cytokine in wound healing, and one which is present at lower concentrations in diabetic wounds. There is also activation of the Ras/MAPK signalling pathway. CONCLUSION: One mechanism through which healing may be stimulated by PBM is via the FGF-Ras/MAPK signalling pathway, although strong evidence under hyperglycaemic conditions is lacking.