Purpose: Mesenchymal stem cells (MSCs) can promote burn wound healing, skin appearance, and function recovery by promoting the differentiation and migration of fibroblasts of a wound. The burn environment can activate the autophagy of MSCs. However, it is not clear whether this autophagy can affect the proliferation and migration of fibroblasts.
Methods: In this study, pretreated MSCs with rapamycin and 3-methyladenine modulated autophagy and co-cultured with fibroblasts of burn. Cell migration was detected by immunofluorescence chemical staining. Western blot analysis and enzyme-linked immunosorbent assay were performed to detect 2,3-Dioxygenase (IDO), cytokine synthesis inhibitory factor 10 (IL-10), cytokine synthesis inhibitory factor 6 (IL-6), prostaglandin E2 (PGE2), transforming growth factor beta 1 (TGF-β1) proteins levels, and the autophagy proteins p62 and microtubule-associated protein LC3-II/I.
Results: We demonstrated that autophagy regulates MSCs survival and proliferation in burn wound transplants and found that autophagy inhibition with 3-methyladenine reduced MSCs-mediated, fibroblast proliferation and migration in burn environment. However, rapamycin-induced autophagy had the opposite effect and increased the TGF-β1 expression. Therefore, we speculate that MSCs may promote fibroblast proliferation and migration by secreting TGF-β1 via the AKT/mTOR (RAC-alpha serine/threonine-protein kinase/mammalian target of rapamycin) pathway.
Conclusion: Autophagy of MSCs regulates burn wound fibroblast proliferation and migration by affecting TGF-β1 and prostaglandin E2 production adjacent to MSCs transplanted on the burn wound. The results of this study provide a potential strategy for promoting MSCs treatment of burns.
Keywords: autophagy; burn wound; mesenchymal stem cell; transforming growth factor β1.
© 2023 The Authors. Skin Research and Technology published by John Wiley & Sons Ltd.