Exosomes Derived from Platelet-Rich Plasma Facilitates Macrophage Mitophagy in Diabetic Wound Healing by Targeting KNG1 via PI3K–AKT Pathway

This study was conducted to investigate the protective effect of platelet-rich plasma-derived exosomes (PRP-Exos) in diabetic wound healing, as well as the involved molecular mechanism. Exosomes collected from PRP were extracted and identified, then the promoting effect on diabetic wound healing was tested in high glucose and lipopolysaccharide (HL)-induced RAW264.7 cells and excisional wound models constructed in streptozotocin-induced diabetic SD rats. PRP-Exos showed the best capacity for accelerating wound healing in the diabetic rat model. Cell proliferation of RAW264.7 cells was effectively facilitated after HL treatment, while PRP-Exos implemented could obviously eliminate the HL effect on RAW264.7 cells. The protein expression levels of PINK1, parkin, and LC3I/LC3II were both obviously diminished, and the expression of kininogen-1 (KNG1) was obviously increased in HL-induced RAW264.7 cells, while the opposite results were observed after PRP-Exos treatment. HL treatment could remarkably suppress the protein expression levels of p-PI3K/PI3K and p-AKT/AKT in RAW264.7 cells, while PRP-Exos administration could reverse this trend. Interestingly, KNG1 upregulation could effectively reverse the effect of PRP-Exos on the tumor necrosis factor-alpha and high mobility histone 1 levels, protein expression of p-PI3K/PI3K and p-AKT/AKT, and mitophagy-related markers in HL-induced RAW264.7 cells. In conclusion, PRP-Exos facilitated macrophage mitophagy in diabetic wound healing by targeting KNG1 via PI3K-AKT pathway.