Mesenchymal Stem Cell-Derived Extracellular Vesicles Protect Human Corneal Endothelial Cells from Endoplasmic Reticulum Stress-Mediated Apoptosis.

间充质干细胞来源的细胞外囊泡保护人角膜内皮细胞免受内质网应激介导的凋亡。

• 影响指数: 6.208
• 发表时间: May 2021 6
• 来源期刊: Int J Mol Sci
• DOI: 10.3390/ijms22094930
• PMID: 34066474
• 文章类型: Journal Article
• 中科院分区: Q2
• 方向: 生物
• 作者列表: Buono L,Scalabrin S,De Iuliis M,Tanzi A,Grange C,Tapparo M,Nuzzi R,Bussolati B

关键词: corneal dystrophy; corneal endothelium; exosomes

Mesh: Apoptosis / drug effects genetics; Cell Separation; Culture Media, Serum-Free; Endoplasmic Reticulum Stress / drug effects genetics; Endothelial Cells / drug effects metabolism pathology; Endothelium, Corneal / pathology; Extracellular Vesicles / drug effects metabolism; Gene Expression Regulation / drug effects; Humans; Mesenchymal Stem Cells / drug effects metabolism; MicroRNAs / genetics metabolism; Phosphorylation / drug effects; Tunicamycin / pharmacology

Abstract

Corneal endothelial dystrophy is a relevant cause of vision loss and corneal transplantation worldwide. In the present study, we analyzed the effect of mesenchymal stem cell (MSC)-derived extracellular vesicles (MSC-EVs) in an in vitro model of corneal dystrophy, characterized by endoplasmic reticulum stress. The effects of MSC-EVs were compared with those of serum-derived EVs, reported to display a pro-angiogenic activity. MSC-EVs were able to induce a significant down-regulation of the large majority of endoplasmic reticulum stress-related genes in human corneal endothelial cells after exposure to serum deprivation and tunicamycin. In parallel, they upregulated the Akt pathway and limited caspase-3 activation and apoptosis. At variance, the effect of the serum EVs was mainly limited to Akt phosphorylation, with minimal or absent effects on endoplasmic reticulum stress modulation and apoptosis prevention. The effects of MSC-EVs were correlated to the transfer of numerous endoplasmic reticulum (ER)-stress targeting miRNAs to corneal endothelial cells. These data suggest a potential therapeutic effect of MSC-EVs for corneal endothelial endoplasmic reticulum stress, a major player in corneal endothelial dystrophy.

摘要

角膜内皮营养不良是世界范围内视力丧失和角膜移植的相关原因。在本研究中,我们分析了间充质干细胞（MSC）衍生的细胞外囊泡（MSC-EV）在角膜营养不良的体外模型中的作用，以内质网应激为特征。将MSC-EV的效果与血清来源的EV的效果进行了比较，据报道显示具有促血管生成活性。暴露于血清剥夺和衣霉素后，MSC-EV能够诱导人角膜内皮细胞中大部分内质网应激相关基因的显着下调。并行,它们上调Akt途径并限制caspase-3的激活和凋亡。在不一致的情况下，血清EV的作用主要限于Akt磷酸化，对内质网应激调节和凋亡预防的影响最小或不存在。MSC-EV的作用与许多内质网（ER）应激靶向miRNA向角膜内皮细胞的转移有关。这些数据表明MSC-EV对角膜内皮内质网应激的潜在治疗作用，角膜内皮营养不良的主要参与者。