Photobiomodulation hastens diabetic wound healing via modulation of the PI3K/AKT/FoxO1 pathway in an adipose derived stem cell-fibroblast co-culture

Abstract

Prolonged inflammation and impaired redox balance are important causes of delayed wound healing. Photobiomodulation (PBM) enhances delayed wound healing by modulating various cellular signaling pathways involved in the wound healing process. This study aimed to reveal the mechanisms of action of PBM in accelerating wound healing in a diabetic adipose derived stem cell (ADSC)-fibroblast co-culture cell model. ADSC-fibroblast co-culture cells were divided into normal (N), normal wounded (NW), diabetic (D) and diabetic wounded (DW) groups and were irradiated (wavelength: 660 or 830 nm; energy density: 5 J/cm²). Unirradiated cells (0 J/cm²) served as controls. Wound closure/migration was recorded in NW and DW groups using light microscopy. Signaling pathway proteins (PI3 kinase, AKT and FoxO1) modulated by PBM were evaluated by immunofluorescence and western blotting. ELISA was used to measure the levels of antioxidants (HMOX1, SOD and CAT). PBM treatment effectively enhanced cell migration and wound closure in irradiated groups. Furthermore, PBM elevated PI3 kinase and AKT signaling proteins that in turn elevated antioxidant levels. These results demonstrate that PBM at 660 and 830 nm increases migration of co-culture cells and is mediated at least in part through the activation/regulation of the PI3K/AKT/FoxO1 signaling pathway. PBM could be a promising therapeutic approach which can be used in chronic wound treatment.