Pathological scarring is the greatest challenge after injury. Exosome from adipose-derived mesenchymal stem cells has been reported effective to improve hypertrophic scar. This study focused on the possible mechanisms during this process. Exosomes from adipose-derived mesenchymal stem cells were extracted first. Hypertrophic scar tissue and paired normal skin tissue were collected from patients. Mice skin incision model and fibroblasts model were established. TGF-β1 was used to stimulate fibroblasts to myofibroblasts transdifferentiation. It was found that exosomes injection could decrease collagen sediment after wound healing. During which, the expression of microRNA-181a decreased. Further, we found that expression of microRNA-181a in scar tissue was higher than in normal skin. Then hypertrophic scar-derived fibroblasts were used for in vitro study. It was found that similar to the use of exosomes, microRNA-181a inhibitor decreased the expression of collagen and α-SMA. While microRNA-181a mimics suppressed the effects of exosomes. During fibroblast to myofibroblast trans-differentiation, level of microRNA-181a well as levels of scar-related molecules also decreased with the use of exosomes and vice versa. SIRT1 was confirmed one of the downstream targets of microRNA-181a. Suppression of SIRT1 led to diminished effects of exosomes in hypertrophic scar derived fibroblasts. In mice skin incision model, injection of SIRT1 inhibitor led to increased collagen synthesis. In conclusion, exosomes from Adipose-derived mesenchymal stem cells are promising to antagonize scarring through the regulation of microRNA-181a/SIRT1 axis.
Keywords: Adipose-derived mesenchymal stem cell; Exosome; Hypertrophic scar; MicroRNA-181a; SIRT1.
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