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BMSC-derived exosomes regulate the Treg/Th17 balance through the miR-21-5p/TLR4/MyD88/NF-κB pathway to alleviate dry eye symptoms in mice

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机构: [1]Yanan Hosp Kunming City, Dept Ophthalmol, Kunming 650051, Yunnan, Peoples R China [2]Kunming Univ Sci & Technol, Peoples Hosp Yunnan Prov 1, Affiliated Hosp, Dept Informat, Kunming 650032, Yunnan, Peoples R China [3]Kunming Med Univ, Dept Ophthalmol, Kunming 650500, Yunnan, Peoples R China
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关键词: Exosomes Dry eye syndrome Treg/Th17 balance miR-21-5p TLR4/MyD88/NF-kappa B pathway

摘要:
Bone marrow mesenchymal stem cell (BMSC)-derived exosomes (BMSC-Exos) have a variety of biological functions and are extensively involved in the regulation of inflammatory diseases, as well as tissue repair and regeneration. However, the mechanism of action of these compounds in dry eye disease (DED) in mice is still unclear. This study demonstrated that the Treg/Th17 ratio was strongly imbalanced in DED clinical samples. BMSC-Exos can modulate the Treg/Th17 balance, improve the integrity of the corneal epithelial layer, and ameliorate DED progression in mice. Mechanistically, BMSC-Exos dramatically decreased the levels of IL-17 and IL-22; increased the levels of IL-4, IL-10, and TGF-beta 1; and increased tear secretion and the number of goblet cells in the conjunctiva in mice, thus alleviating the progression of DED. This effect is achieved by BMSC-Exos through the delivery of miR-21-5p to target and restrain TLR4, thereby restraining the MyD88/NF-kappa B pathway. Our study showed that the upregulation of miR-21-5p in BMSC-Exos may be a therapeutic target for DED. These findings support new ideas and a basis for treating DED, as well as for further study of the application value of exosomes in alleviating DED.

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大类 | 4 区 生物学
小类 | 4 区 细胞生物学 4 区 发育生物学
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出版当年[2023]版:
Q4 CELL BIOLOGY Q4 DEVELOPMENTAL BIOLOGY
最新[2023]版:
Q4 CELL BIOLOGY Q4 DEVELOPMENTAL BIOLOGY

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第一作者机构: [1]Yanan Hosp Kunming City, Dept Ophthalmol, Kunming 650051, Yunnan, Peoples R China
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