Umbilical Cord Mesenchymal Stem Cell-Derived Small Extracellular Vesicles Deliver miR-21 to Promote Corneal Epithelial Wound Healing through PTEN/PI3K/Akt Pathway.
Umbilical Cord Mesenchymal Stem Cell-Derived Small Extracellular Vesicles Deliver miR-21 to Promote Corneal Epithelial Wound Healing through PTEN/PI3K/Akt Pathway.
复制标题
DOI：
10.1155/2022/1252557
复制
发表时间：
2022
影响因子：
4.3
通讯作者：
Zhang H
中科院分区：
文献类型：
--
作者：
Liu X;Li X;Wu G;Qi P;Zhang Y;Liu Z;Li X;Yu Y;Ye X;Li Y;Yang D;Teng Y;Shi C;Jin X;Qi S;Liu Y;Wang S;Liu Y;Cao F;Kong Q;Wang Z;Zhang H
损伤后角膜上皮完整性的快速恢复对于保持角膜透明度和视力特别重要。骨髓间充质干细胞（Mesenchymal stem cells，MSCs）具有多种有效成分，可作为促进创伤愈合的再生治疗剂。骨髓间充质干细胞形成的细胞外囊泡，特别是exosome，被认为是重要的旁分泌介质，通过将microRNA转移到受体细胞中。本研究探讨了人脐带间充质干细胞来源的小细胞外囊泡（HUMSC-sEVs）对角膜上皮创伤愈合的作用机制。 HUMSC-sEV通过透射电子显微镜、纳米颗粒跟踪分析和蛋白质印迹鉴定。在角膜机械创伤模型中评价角膜荧光素染色和组织学染色。通过CCK-8和EdU测定评价HUMSC-sEV或miR-21模拟物处理后HCEC增殖的变化，同时通过体外划痕试验评估迁移。进行全长转录组测序以鉴定与HUMSC-sEV治疗相关的差异表达基因，然后通过实时PCR和Western印迹进行验证。 来源于HUMSC的sEV可以显着促进体外角膜上皮细胞增殖、迁移和体内角膜上皮伤口愈合。miR-21转染后获得了类似的效果，而HUMSC-sEV的有益效果被miR-21敲低部分抵消。结果还表明，这些益处与HCECs中PTEN水平降低和PI 3 K/Akt信号通路激活有关。 HUMSC-sEVs可通过转移miR-21抑制PTEN表达，促进角膜上皮创伤的修复，有望成为一种新型的角膜创伤修复治疗药物。
Rapid restoration of corneal epithelium integrity after injury is particularly important for preserving corneal transparency and vision. Mesenchymal stem cells (MSCs) can be taken into account as the promising regenerative therapeutics for improvement of wound healing processes based on the variety of the effective components. The extracellular vesicles form MSCs, especially exosomes, have been considered as important paracrine mediators though transferring microRNAs into recipient cell. This study investigated the mechanism of human umbilical cord MSC-derived small extracellular vesicles (HUMSC-sEVs) on corneal epithelial wound healing. HUMSC-sEVs were identified by transmission electron microscopy, nanoparticle tracking analysis, and Western blot. Corneal fluorescein staining and histological staining were evaluated in a corneal mechanical wound model. Changes in HCEC proliferation after HUMSC-sEVs or miR-21 mimic treatment were evaluated by CCK-8 and EdU assays, while migration was assessed by in vitro scratch wound assay. Full-length transcriptome sequencing was performed to identify the differentially expressed genes associated with HUMSC-sEVs treatment, followed by validation via real-time PCR and Western blot. The sEVs derived from HUMSCs can significantly promote corneal epithelial cell proliferation, migration in vitro, and corneal epithelial wound healing in vivo. Similar effects were obtained after miR-21 transfection, while the beneficial effects of HUMSC-sEVs were partially negated by miR-21 knockdown. Results also show that the benefits are associated with decreased PTEN level and activated the PI3K/Akt signaling pathway in HCECs. HUMSC-sEVs could enhance the recovery of corneal epithelial wounds though restraining PTEN by transferring miR-21 and may represent a promising novel therapeutic agent for corneal wound repair.
登录
查看更多内容
影响因子：
4.5
作者：
Albanese M;Chen YA;Hüls C;Gärtner K;Tagawa T;Mejias-Perez E;Keppler OT;Göbel C;Zeidler R;Shein M;Schütz AK;Hammerschmidt W
通讯作者：
Hammerschmidt W
DOI：
10.12717/dr.2017.21.1.001
发表时间：
2017-03
期刊：
Development & reproduction
影响因子：
--
作者：
Kim HJ;Park JS
通讯作者：
Park JS
褪黑素刺激的 MSC 衍生的外泌体通过靶向 PTEN/AKT 通路调节巨噬细胞 M1 和 M2 极化，改善糖尿病伤口愈合
影响因子：
7.5
作者：
Liu, Wei;Yu, Muyu;Yang, Lili
通讯作者：
Yang, Lili
影响因子：
64.5
作者：
LEE, RC;FEINBAUM, RL;AMBROS, V
通讯作者：
AMBROS, V
影响因子：
4.5
作者：
Inukai, Sachi;Pincus, Zachary;Slack, Frank J.
通讯作者：
Slack, Frank J.