Exosomes from mmu_circ_0001359-Modified ADSCs Attenuate Airway Remodeling by Enhancing FoxO1 Signaling-Mediated M2-like Macrophage Activation
Exosomes from mmu_circ_0001359-Modified ADSCs Attenuate Airway Remodeling by Enhancing FoxO1 Signaling-Mediated M2-like Macrophage Activation
复制标题
mmu_circ_0001359-修饰的 ADSC 外泌体通过增强 FoxO1 信号介导的 M2 样巨噬细胞激活来减弱气道重塑
DOI：
10.1016/j.omtn.2019.10.049
复制
发表时间：
2020-03-06
影响因子：
8.8
通讯作者：
Bai, Chong
中科院分区：
文献类型：
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作者：
Shang, Yan;Sun, Yahong;Bai, Chong
哮喘是最常见的慢性疾病，以气道重塑和慢性炎症为特征。越来越多的研究发现，巨噬细胞的活化和M1表型转化在哮喘的进展，包括气道重塑中发挥重要作用。然而，M1巨噬细胞向M2表型的逆转已显示减弱气道重塑。外泌体是源自内体的纳米尺寸的细胞外囊泡;它们通过生物活性货物（例如蛋白质、酶、核酸（microRNA [miRNA]、mRNA、DNA）和代谢物）的细胞内转移在控制生理和病理条件中发挥直接作用。然而，转移机制尚不清楚。为了揭示潜在的治疗机制，我们构建了卵白蛋白诱导的哮喘小鼠模型和脂多糖诱导的RAW 264.7巨噬细胞。高通量测序显示，与正常小鼠相比，mmu_circ_0001359在哮喘小鼠中下调。脂肪源性干细胞（ADSC）-外泌体治疗抑制炎症细胞因子的表达M1巨噬细胞转化为M2表型，脂多糖诱导的条件下。与野生型外泌体相比，在细胞因子表达方面，来自ADSC中mmu_circ_0001359过表达的外泌体增加了治疗效果。荧光素酶报告基因测定证实，来自mmu_circ_0001359修饰的ADSC的外来体通过海绵状miR-183- 5 p增强Fox 01信号传导介导的M2样巨噬细胞活化来减弱气道重塑。总之，mmu_circ_0001359富集的外泌体通过促进M2样巨噬细胞来减弱气道重塑。
Asthma is the most common chronic disease and is characterized by airway remodeling and chronic inflammation. Increasingly, studies have found that the activation and M1 phenotypic transformation of macrophages play important roles in asthma progress, including airway remodeling. However, the reversal of M1 macrophages to the M2 phenotype has been shown to attenuate airway remodeling. Exosomes are nano-sized extracellular vesicles derived from endosomes; they play direct roles in governing physiological and pathological conditions by the intracellular transfer of bioactive cargo, such as proteins, enzymes, nucleic acids (microRNA [miRNA], mRNA, DNA), and metabolites. However, transfer mechanisms are unclear. To uncover potential therapeutic mechanisms, we constructed an ovalbumin-induced asthma mouse model and lipopolysac-charide-induced RAW264.7 macrophages cells. High-throughput sequencing showed that mmu_circ_0001359 was downregulated in asthmatic mice when compared with normal mice. Adipose-derived stem cell (ADSC)-exosome treatment suppressed inflammatory cytokine expression by the conversion of M1 macrophages to the M2 phenotype, under lipopolysaccharide-induced conditions. Exosomes from mmu_circ_0001359 overexpression in ADSCs increased therapeutic effects, in terms of cytokine expression, when compared with wild-type exosomes. Luciferase reporter assays confirmed that exosomes from mmu_circ_0001359-modified ADSCs attenuated airway remodeling by enhancing Fox01 signaling-mediated M2-like macrophage activation, via sponging miR-183-5p. In conclusion, mmu_circ_0001359-enriched exosomes attenuated airway remodeling by promoting M2-like macrophages.