Inflammatory bowel diseases (IBDs), such as Crohn's disease and ulcerative colitis, are chronic inflammatory disorders of the gastrointestinal tract. Although IBDs increase the risk of colitis‐associated colon cancer, the underlying mechanisms are not fully understood. Extracellular vesicles (EVs) are lipid‐bound sacs that transport proteins, RNA, and lipids between cells and are key mediators of cellular communication in both physiological and pathological settings. EVs have been implicated in many cancer hallmarks, including uncontrolled tumor growth and metastasis. In this study, we investigated the effects of colon‐derived EVs on the proliferation of fibroblasts. We used comparative proteomics to characterize protein profiles of colorectal EVs isolated from healthy mice (Con‐EVs) and those with dextran sulfate sodium‐induced colitis (IBD‐EVs). The results showed that 109 proteins were upregulated in IBD‐EVs. Notably, expression of epidermal growth factor receptor (EGFR), which plays important roles in cell proliferation and development, was increased in IBD‐EVs. We then examined the effect of EVs on murine NIH3T3 fibroblasts and found that IBD‐EVs significantly promoted cell proliferation in EGFR‐ and ERK‐dependent manner. Our findings suggest that inflamed colon‐derived EVs promote tumor development thorough activation of fibroblasts.

中文翻译：

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来自发炎的鼠大肠组织的细胞外囊泡通过表皮生长因子受体诱导成纤维细胞增殖

克罗恩氏病和溃疡性结肠炎等炎症性肠病（IBD）是胃肠道的慢性炎症性疾病。尽管IBDs增加了与结肠炎相关的结肠癌的风险，但是其潜在机制尚未完全被理解。细胞外囊泡（EVs）是脂质结合的囊，在细胞之间运输蛋白质，RNA和脂质，是生理和病理情况下细胞通讯的关键介质。电动汽车已牵涉到许多癌症标志，包括不受控制的肿瘤生长和转移。在这项研究中，我们调查了结肠电动车对成纤维细胞增殖的影响。我们使用比较蛋白质组学来表征从健康小鼠（Con-EV）和硫酸右旋糖酐钠诱发的结肠炎（IBD-EV）分离的结直肠电动汽车的蛋白质谱。结果表明，IBD-EVs中有109种蛋白被上调。值得注意的是，在细胞增殖和发育中起重要作用的表皮生长因子受体（EGFR）的表达在IBD-EV中有所增加。然后，我们检查了电动汽车对鼠NIH3T3成纤维细胞的影响，发现IBD-电动汽车以EGFR和ERK依赖性方式显着促进了细胞增殖。我们的发现表明，发炎的结肠源性电动车可通过激活成纤维细胞来促进肿瘤的发展。在细胞增殖和发育中起重要作用的蛋白质在IBD-EV中有所增加。然后，我们检查了电动汽车对鼠NIH3T3成纤维细胞的影响，发现IBD-电动汽车以EGFR和ERK依赖性方式显着促进了细胞增殖。我们的发现表明，发炎的结肠源性电动车可通过激活成纤维细胞来促进肿瘤的发展。在细胞增殖和发育中起重要作用的蛋白质在IBD-EV中有所增加。然后，我们检查了电动汽车对鼠NIH3T3成纤维细胞的影响，发现IBD-电动汽车以EGFR和ERK依赖性方式显着促进了细胞增殖。我们的发现表明，发炎的结肠源性电动车可通过激活成纤维细胞来促进肿瘤的发展。