Microrna-3100 From Bone Marrow Mesenchymal Stem Cells (Bmscs) Exosomes Alleviates Autoimmune Arthritis In Mice Via Regulating Forkhead Box P3 Acetylase
JOURNAL OF BIOMATERIALS AND TISSUE ENGINEERING(2021)
Abstract
To study the effect and mechanism of microRNA-3100 from exosome of BMSCs on autoimmune arthritis in mice. CIA mice model was established and treated with BMSCs exosomes or DMSO. The expression of Foxp3 was detected by PCR and Western blot. The Treg/Th17 population of T cells and the expression of related inflammatory factors were analyzed by flow cytometry. BMSCs transfected with MicroRNA-3100 inhibitor or MicroRNA-3100 was used to treat CIA mice through intravenous injection. The levels of Foxp3 and its acetylation, Treg/Th17 differentiation and inflammatory factors were detected, and the synovial tissues of mice were collected for analysis of its inflammatory infiltration. RA rats exhibited down-regulated Treg population and increased Th17 population in PBMC and SF, accompanied by reduced Foxp3 and acetylated Foxp3 expression, suppressed Tip-60 expression in SF, in relative to normal control. However, exosomes of BMSCs administration recovered the changes. Further result showed that exosomes from BMSCs was enriched for miR-3100. miR-3100 inhibitor exposed CD4(+) T cell exhibited reduced Tip60 and acetylated-Foxp3 expression, decreased Tregs population and increased Th17 cell population, vice versa as the miR-3100 mimics does. In addition, Tip60 inhibitors NU905 exerted the same effect as miR-3100 inhibitor transfection dose. Finally, miR-3100 overexpression could significantly reduce inflammation and immune cell infiltration, correct the dysfunction between Th17 and Tregs, recovered Tip60 and acetylation Foxp3 expression. MiRNA-3100 is enriched in exosomes of BMSCs, and can up-regulate the expression of Foxp3, acetylated Foxp3 and Tip60 level, improving the imbalance of Treg/Th17 ratio, and improve autoimmune arthritis in mice.
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Key words
Exosomes, Bone Marrow Mesenchymal Stem Cells, Acetylase, Autoimmune Arthritis
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