Exosomal miR-135a derived from human amnion mesenchymal stem cells promotes cutaneous wound healing in rats and fibroblast migration by directly inhibiting LATS2 expression
Exosomal miR-135a derived from human amnion mesenchymal stem cells promotes cutaneous wound healing in rats and fibroblast migration by directly inhibiting LATS2 expression
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人羊膜间充质干细胞来源的外泌体miR-135a通过直接抑制LATS2表达促进大鼠皮肤伤口愈合和成纤维细胞迁移
DOI：
10.1186/s13287-020-1570-9
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发表时间：
2020-02-13
影响因子：
7.5
通讯作者：
Qi, Jianping
中科院分区：
文献类型：
--
作者：
Gao, Shaoying;Chen, Tao;Qi, Jianping
背景创伤愈合是一个复杂的病理生理过程，涉及多种细胞和细胞因子。在本研究中，我们发现将人羊膜间充质干细胞局部注射到大鼠伤口中可以促进伤口愈合。因此，我们假设人羊膜间充质干细胞的外泌体含有调节表皮细胞迁移的物质。已有报道miR-135 a参与细胞迁移和转化。然而，还没有关于其在皮肤伤口愈合中的作用的报道。方法为了验证这一假设，我们将过表达miR-135 a的外泌体直接注射到伤口边缘。此外，我们在体外测试了miR-135 a过表达或敲低的BJ细胞的迁移。此外，使用Western印迹分析来检测用miR-135 a过表达或敲低处理后成纤维细胞迁移相关蛋白的表达。结果与对照组相比，MiR-135 a能显著促进创面愈合。Western blot分析显示miR-135 a过表达后LATS 2表达显著下调。此外，miR-135 a的敲低有效地减弱了外泌体对细胞迁移的促进作用。结论miR-135 a促进创伤愈合可能是通过下调LATS 2水平，增加细胞迁移而实现的。本研究为来源于人羊膜间充质干细胞的外泌体中miR-135 a对伤口愈合的治疗作用提供了理论基础。
Background Wound healing is a complex pathophysiological process that involves a variety of cells and cytokines. In this study, we found that local injection of human amnion mesenchymal stem cells into wounds in rats could promote wound healing. Therefore, we hypothesized that the exosomes of human amnion mesenchymal stem cells contain substances that regulate the migration of epidermal cells. It has been reported that miR-135a is involved in cell migration and transformation. However, there have been no reports of its function in skin wound healing. Methods To test this hypothesis, we injected exosomes overexpressing miR-135a directly into the wound margin. In addition, we tested the migration of BJ cells with overexpression or knockdown of miR-135a in vitro. Additionally, Western blot analysis was used to detect the expression of fibroblast migration-associated proteins after treatment with miR-135a overexpression or knockdown. Results MiR-135a significantly promoted wound healing compared to the control treatment. Western blot analysis showed a significant downregulation of LATS2 after overexpression of miR-135a. In addition, knockdown of miR-135a effectively attenuated the promoting effect of exosomes on cell migration. Conclusions Our results indicated that miR-135a promotes wound healing, which may be mediated by downregulating LATS2 levels to increase cell migration. This study provides a rationale for the therapeutic effect on wound healing of miR-135a in exosomes derived from human amnion mesenchymal stem cells.