Zhao Bin, Li Xiaodong, Shi Xiaomin, Shi Xueqin, Zhang Wei, Wu Gaofeng, Wang Xujie, Su Linlin, Hu Dahai
Department of Burns and Cutaneous Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, Shannxi 710032, China.
School of Life Sciences, Northwestern Polytechnical University, Xi'an, Shannxi 710072, China.
Stem Cells Int. 2018 Jul 25;2018:5420463. doi: 10.1155/2018/5420463. eCollection 2018.
Previous work in our laboratory demonstrated that exosomes derived from human amniotic epithelial cells (hAECs) accelerated wound healing by promoting the proliferation and migration of fibroblasts. It is reported that exosomes, which are carriers of the microRNAs (miRNAs) and proteins, play an important role in the regulation of cell-to-cell communication. However, it is still unclear precisely which molecule or which group of molecules carried within hAEC-derived exosomes (hAEC-Exos) mediated wound healing. Here, we explored purified hAEC-Exos together with either proteinase K (PROse) or RNase A on the effect of fibroblasts and cutaneous wound healing. Our experiments demonstrated that hAEC-Exos were positive for exosomal markers CD9, CD63, and CD81. Also, we found that hAEC-Exos could be internalized by fibroblasts and then stimulated cell migration and proliferation. However, the promotive effect of hAEC-Exos was abolished by pretreating hAEC-Exos with RNase A, not PROse. Importantly, wound healing assay showed that local injection of hAEC-Exos or PROse pretreated hAEC-Exos at skin wounds significantly accelerated wound healing. Our findings revealed an important role of exosomal miRNAs in wound healing.
我们实验室之前的研究表明，源自人羊膜上皮细胞（hAECs）的外泌体通过促进成纤维细胞的增殖和迁移来加速伤口愈合。据报道，作为微小RNA（miRNAs）和蛋白质载体的外泌体在细胞间通讯调节中发挥着重要作用。然而，目前仍不清楚hAEC衍生的外泌体（hAEC-Exos）中究竟是哪种分子或哪组分子介导了伤口愈合。在此，我们研究了用蛋白酶K（PROse）或核糖核酸酶A处理纯化的hAEC-Exos后对成纤维细胞和皮肤伤口愈合的影响。我们的实验表明，hAEC-Exos的外泌体标志物CD9、CD63和CD81呈阳性。此外，我们发现hAEC-Exos可以被成纤维细胞内化，进而刺激细胞迁移和增殖。然而，用核糖核酸酶A而非蛋白酶K预处理hAEC-Exos后，其促进作用被消除。重要的是，伤口愈合试验表明，在皮肤伤口局部注射hAEC-Exos或经PROse预处理的hAEC-Exos可显著加速伤口愈合。我们的研究结果揭示了外泌体miRNAs在伤口愈合中的重要作用。
