Gu Li, Ren Feng, Fang Xianrui, Yuan Lianwen, Liu Ganglei, Wang Shalong
Department of Gastroenterology, The Second Xiangya Hospital of Central South University, Changsha, China.
Department of General Surgery, The Second Xiangya Hospital of Central South University, Changsha, China.
Front Med (Lausanne). 2021 Jun 24;8:660614. doi: 10.3389/fmed.2021.660614. eCollection 2021.
Mesenchymal stem cell (MSC)-derived exosomes (Exos) are recently proved to be a promising candidate for ulcerative colitis (UC), but the mechanism remains unclear. We investigated the effects of MSC-derived exosomal microRNA-181a (miR-181a) on gut microbiota, immune responses, and intestinal barrier function in UC. Human bone marrow MSC-derived Exos were extracted and identified transmission electron microscopy (TEM), Nanoparticle Tracking Analysis (NTA), and Western blotting. Dextran sodium sulfate (DSS)-induced colitis model and lipopolysaccharide (LPS)-induced human colonic epithelial cell (HCOEPIC) model were established to determine the effect of MSC-Exos on gut microbiota, immune responses, and intestinal barrier function and . The relationship between miR-181a and UC was analyzed using the Gene Expression Omnibus (GEO) database. MSC-miR-181-inhibitor was used to reveal the role of exosomal miR-181a in DSS-induced colitis. TEM and NTA results showed that Exos of a diameter of about 100 nm with the round and oval vesicle-like structure were successfully extracted. The expressions of the CD63, CD81, and TSG101 proteins were positive in these Exos. After MSC-Exo treatment, the colon length in colitis mice increased; colon inflammatory injury decreased; TNF-α, IL-6, IL-1β, IL-17, and IL-18 levels decreased; and Claudin-1, ZO-1, and IκB levels increased. In addition, the structure of the gut microbiota in DSS-induced colitis mice was changed by MSC-Exos. MSC-Exos showed antiapoptotic effects on LPS-induced HCOEPIC. The protective effects decreased significantly by treatment with MSC-Exos interfered with miR-181a inhibitor and . MSC-derived exosomal miR-181a could alleviate experimental colitis by promoting intestinal barrier function. It exerted anti-inflammatory function and affected the gut microbiota. This indicated that MSC exosomal miR-181a may exhibit potential as a disease-modifying drug for UC.
间充质干细胞（MSC）来源的外泌体（Exos）最近被证明是治疗溃疡性结肠炎（UC）的一种有前景的候选物，但其机制仍不清楚。我们研究了MSC来源的外泌体微小RNA-181a（miR-181a）对UC中肠道微生物群、免疫反应和肠道屏障功能的影响。通过透射电子显微镜（TEM）、纳米颗粒跟踪分析（NTA）和蛋白质印迹法提取并鉴定了人骨髓MSC来源的Exos。建立葡聚糖硫酸钠（DSS）诱导的结肠炎模型和脂多糖（LPS）诱导的人结肠上皮细胞（HCOEPIC）模型，以确定MSC-Exos对肠道微生物群、免疫反应和肠道屏障功能的影响。使用基因表达综合数据库（GEO）分析miR-181a与UC之间的关系。使用MSC-miR-181抑制剂揭示外泌体miR-181a在DSS诱导的结肠炎中的作用。TEM和NTA结果表明，成功提取了直径约100nm、具有圆形和椭圆形囊泡样结构的Exos。这些Exos中CD63、CD81和TSG101蛋白的表达呈阳性。MSC-Exo治疗后，结肠炎小鼠的结肠长度增加；结肠炎症损伤减轻；肿瘤坏死因子-α、白细胞介素-6、白细胞介素-1β、白细胞介素-17和白细胞介素-18水平降低；紧密连接蛋白-1、闭锁小带蛋白-1和核因子κB抑制蛋白水平升高。此外，MSC-Exos改变了DSS诱导的结肠炎小鼠的肠道微生物群结构。MSC-Exos对LPS诱导的HCOEPIC具有抗凋亡作用。用MSC-Exos干扰miR-181a抑制剂处理后，保护作用显著降低。MSC来源的外泌体miR-181a可通过促进肠道屏障功能减轻实验性结肠炎。它发挥抗炎功能并影响肠道微生物群。这表明MSC外泌体miR-181a可能作为一种改善UC病情的药物展现出潜力。
Zotero 插件
