Division of Metabolism and Biosystemic Science, Gastroenterology, And Hematology/Oncology, Department of Medicine, Asahikawa Medical University, Asahikawa 078-8510, Japan.
Department of Gastroenterology and Advanced Medical Sciences, Asahikawa Medical University, Asahikawa 078-8510, Japan.
Mediators Inflamm. 2021 Mar 29;2021:5582943. doi: 10.1155/2021/5582943. eCollection 2021.
Inflammatory bowel disease (IBD), such as ulcerative colitis (UC) and Crohn's disease (CD), is an intractable intestinal inflammation associated with the disruption of the intestinal mucosa. We previously demonstrated that -derived long-chain polyphosphate (poly P) improved the intestinal barrier function by the upregulation of cell adhesion and relieved intestinal inflammation, thereby exerting a curing effect on colitis , , and in an investigator-initiated clinical study of UC. However, how poly P improves mucosal defects induced by intestinal inflammation has not been elucidated. In this study, we detected the accumulation of platelets in inflamed tissues induced by poly P in a dextran sulfate sodium- (DSS-) induced colitis mouse model. A light transmission aggregometry analysis and scanning electron microscopy showed that poly P promoted the platelet aggregation. An SRB assay and ki-67 staining showed that the supernatant of poly P-treated platelet-rich plasma (PRP) increased intestinal epithelial cell growth. A wound healing assay showed that the supernatant of poly P-treated PRP, but not poly P itself, accelerated wound healing. A Western blotting analysis indicated that mitogen-activated protein kinase activation was induced by the supernatant of poly P-treated human PRP in the epithelial cells and its wound healing effect was significantly decreased by the inhibition of ERK signaling. These data suggested that platelet-derived mediators induced by poly P improved intestinal inflammation through the promotion of epithelial cell growth by the activation of the ERK signaling pathway. The mechanism is a novel host-microbe interaction through mammalian platelet-derived mediators induced by bacterial molecules.
炎症性肠病（IBD），如溃疡性结肠炎（UC）和克罗恩病（CD），是一种与肠黏膜破坏相关的难治性肠道炎症。我们之前的研究表明，来源于的长链多聚磷酸盐（poly P）通过上调细胞黏附来改善肠道屏障功能，并缓解肠道炎症，从而对结肠炎产生治疗作用，在溃疡性结肠炎的研究者发起的临床研究中也是如此。然而，poly P 如何改善肠道炎症引起的黏膜缺陷尚未阐明。在这项研究中，我们在葡聚糖硫酸钠（DSS）诱导的结肠炎小鼠模型中检测了 poly P 在诱导炎症组织中血小板的积累。透光比浊分析和扫描电子显微镜显示，poly P 促进了血小板的聚集。SRB 分析和 ki-67 染色显示，poly P 处理的富含血小板的血浆（PRP）上清液促进了肠道上皮细胞的生长。伤口愈合试验表明，poly P 处理的 PRP 上清液而非 poly P 本身可加速伤口愈合。Western blot 分析表明，poly P 处理的人 PRP 上清液诱导了上皮细胞中丝裂原活化蛋白激酶的激活，而 ERK 信号通路的抑制显著降低了其伤口愈合作用。这些数据表明，poly P 诱导的血小板衍生介质通过激活 ERK 信号通路促进上皮细胞生长来改善肠道炎症。该机制是一种通过细菌分子诱导哺乳动物血小板衍生介质的新型宿主-微生物相互作用。
