TY - JOUR TI - miR-100-5p in human umbilical cord mesenchymal stem cell–derived exosomes mediates eosinophilic inflammation to alleviate atherosclerosis via the FZD5/Wnt/β-catenin pathway AU - Gao, Heng AU - Yu, Zhanbiao AU - Li, Yuanyuan AU - Wang, Xue T2 - Acta Biochimica et Biophysica Sinica AB - Exosomes derived from human umbilical cord mesenchymal stem cells (hUMSC-Ex) play important roles in immune and inflammation diseases. However, the role of hUMSC-Ex in atherosclerosis has not been elucidated. In this study, the isolated exosomes were identified by transmission electron microscopy and nanoparticle tracking analysis. Exosome marker protein levels were increased in the hUMSC-Ex compared with those in hUMSC suspension, indicating that exosomes were successfully isolated from hUMSCs. Furthermore, eosinophils were treated with oxidized low-density lipoprotein (ox-LDL) to construct inflammation model and then incubated with hUMSC-Ex derived from hUMSCs which were transfected with miR-100-5p mimic or miR-100-5p inhibitor. We found that hUMSC-Ex increased miR-100-5p expression, inhibited cell migration, promoted cell apoptosis, and reduced inflammatory cytokine levels in ox-LDL-treated eosinophils, and miR-100-5p overexpression in hUMSCs enhanced these effects, while miR-100-5p inhibition reversed these effects. Moreover, frizzled 5 (FZD5) was a target gene of miR-100-5p. FZD5 overexpression reversed the inhibitory effects of hUMSC-Ex-miR-100-5p on cell progression and inflammation in eosinophils. Additionally, hUMSC-Ex-miR-100-5p decreased the expression of cyclin D1 and β-catenin proteins. Wnt/β-catenin pathway activator BML-284 effectively reversed the effects of hUMSC-Ex-miR-100-5p on cell progression and inflammation in eosinophils. ApoE−/− mice were fed with high-fat diet to construct an atherosclerosis mice model, and hUMSC-Ex was injected into mice. HUMSC-Ex reduced atherosclerotic plaque area and inflammation response in atherosclerosis mice. This study demonstrates that hUMSC-Ex-miR-100-5p inhibits cell progression and inflammatory response in eosinophils via the FZD5/Wnt/β-catenin pathway, thereby alleviating atherosclerosis progression. DA - 2021/07/13/ PY - 2021 DO - 10.1093/abbs/gmab093 DP - Silverchair IS - gmab093 J2 - Acta Biochimica et Biophysica Sinica SN - 1745-7270 UR - https://doi.org/10.1093/abbs/gmab093 Y2 - 2021/07/13/18:30:18 ER -