MicroRNAs of extracellular vesicles derived from mesenchymal stromal cells alleviate inflammation in dry eye disease by targeting the IRAK1/ TAB2/NF-cB pathway
机构：[1]Beijing Institute of Ophthalmology, Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing Key Laboratory of Ophthalmology and Visual Sciences, Beijing, 100005, China首都医科大学附属北京同仁医院首都医科大学附属同仁医院[2]Cell Therapy Center, Beijing Institute of Geriatrics, Xuanwu Hospital Capital Medical University, National Clinical Research Center for Geriatric Diseases, And Key Laboratory of Neurodegenerative Diseases, Ministry of Education, Beijing, 100053, China内科系统科技平台老年医学科神经变性病教育部重点实验室首都医科大学宣武医院
Purpose: To investigate the efficacy and mechanisms of human umbilical cord-derived MSC-derived extracellular vesicles (hucMSC-EVs) in a mouse model of desiccation-induced dry eye disease (DED).Methods: hucMSC-EVs were enriched by ultracentrifugation. The DED model was induced by desiccating envi-ronment combined with scopolamine administration. The DED mice were divided into the hucMSC-EVs group, fluorometholone (FML) group, PBS group, and blank control group. Tear secretion, corneal fluorescein staining, the cytokine profiles in tears and goblet cells, TUNEL-positive cell, and CD4+ cells were examined to assess therapeutic efficiency. The miRNAs in the hucMSC-EVs were sequenced, and the top 10 were used for miRNA enrichment analysis and annotation. The targeted DED-related signaling pathway was further verified by using RT-qPCR and western blotting.Results: Treatment with hucMSC-EVs increased the tear volume and maintained corneal integrity in DED mice. The cytokine profile in the tears of the hucMSC-EVs group presented with a lower level of proinflammatory cytokines than PBS group. Moreover, hucMSC-EVs treatment increased goblet cell density and inhibited cell apoptosis and CD4+ cell infiltration. Functional analysis of the top 10 miRNAs in hucMSC-EVs showed a high correlation with immunity. Among them, miR-125 b, let-7b, and miR-6873 were conserved between humans and mice and were associated with the IRAK1/TAB2/NF-cB pathway that was activated in DED. Furthermore, IRAK1/TAB2/NF-cB pathway activation and the abnormal expression of IL-4, IL-8, IL-10, IL-13, IL-17, and TNF-a were reversed by hucMSC-EVs.Conclusions: hucMSCs-EVs alleviate DED signs, suppress inflammation and restore homeostasis of the corneal surface by multitargeting the IRAK1/TAB2/NF-cB pathway via certain miRNAs.
基金：
National Natural Science Foundation of China [81970765, 82171250, 81973351]
第一作者机构：[1]Beijing Institute of Ophthalmology, Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing Key Laboratory of Ophthalmology and Visual Sciences, Beijing, 100005, China
共同第一作者：
通讯作者：
通讯机构：[1]Beijing Institute of Ophthalmology, Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing Key Laboratory of Ophthalmology and Visual Sciences, Beijing, 100005, China[2]Cell Therapy Center, Beijing Institute of Geriatrics, Xuanwu Hospital Capital Medical University, National Clinical Research Center for Geriatric Diseases, And Key Laboratory of Neurodegenerative Diseases, Ministry of Education, Beijing, 100053, China[*1]Beijing Institute of Ophthalmology, Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing Key Laboratory of Ophthalmology and Visual Sciences, Beijing, 100005, China[*2]Cell Therapy Center, Beijing Institute of Geriatrics, Xuanwu Hospital Capital Medical University, National Clinical Research Center for Geriatric Diseases, And Key Laboratory of Neurodegenerative Diseases, Ministry of Education, Beijing, 100053, China.
推荐引用方式(GB/T 7714)：
Wang Leying,Wang Xueyao,Chen Qiankun,et al.MicroRNAs of extracellular vesicles derived from mesenchymal stromal cells alleviate inflammation in dry eye disease by targeting the IRAK1/ TAB2/NF-cB pathway[J].OCULAR SURFACE.2023,28:131-140.doi:10.1016/j.jtos.2023.03.002.
APA：
Wang, Leying,Wang, Xueyao,Chen, Qiankun,Wei, Zhenyu,Xu, Xizhan...&Liang, Qingfeng.(2023).MicroRNAs of extracellular vesicles derived from mesenchymal stromal cells alleviate inflammation in dry eye disease by targeting the IRAK1/ TAB2/NF-cB pathway.OCULAR SURFACE,28,
MLA：
Wang, Leying,et al."MicroRNAs of extracellular vesicles derived from mesenchymal stromal cells alleviate inflammation in dry eye disease by targeting the IRAK1/ TAB2/NF-cB pathway".OCULAR SURFACE 28.(2023):131-140
医学