Department of burn and injury, Second Affiliated Hospital of Kunming Medical University, Kunming City, China.
Skin Res Technol. 2023 Aug;29(8):e13431. doi: 10.1111/srt.13431.
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.
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.
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.
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.
间充质干细胞（MSCs）通过促进伤口成纤维细胞的分化和迁移来促进烧伤创面愈合、皮肤外观和功能恢复。烧伤环境可以激活 MSCs 的自噬。然而，尚不清楚这种自噬是否会影响成纤维细胞的增殖和迁移。
本研究通过雷帕霉素和 3-甲基腺嘌呤预处理 MSCs 调节自噬，并与烧伤的成纤维细胞共培养。通过免疫荧光化学染色检测细胞迁移。Western blot 分析和酶联免疫吸附试验检测 2,3-二氧代戊二酸（IDO）、细胞因子合成抑制因子 10（IL-10）、细胞因子合成抑制因子 6（IL-6）、前列腺素 E2（PGE2）、转化生长因子β 1（TGF-β1）蛋白水平以及自噬蛋白 p62 和微管相关蛋白 LC3-II/I。
我们证明自噬调节 MSCs 在烧伤创面移植中的存活和增殖，并发现用 3-甲基腺嘌呤抑制自噬会减少 MSCs 在烧伤环境中对成纤维细胞的增殖和迁移的作用。然而，雷帕霉素诱导的自噬则产生相反的效果，增加了 TGF-β1 的表达。因此，我们推测 MSCs 可能通过 AKT/mTOR（RAC-alpha 丝氨酸/苏氨酸蛋白激酶/哺乳动物雷帕霉素靶蛋白）途径分泌 TGF-β1 来促进成纤维细胞的增殖和迁移。
MSCs 的自噬通过影响 TGF-β1 和 PGE2 的产生来调节烧伤创面附近的成纤维细胞的增殖和迁移。这项研究的结果为促进 MSCs 治疗烧伤提供了一种潜在的策略。
