Human β-defensin-3 promotes intestinal epithelial cell migration and reduces the development of necrotizing enterocolitis in a neonatal rat model
Human β-defensin-3 promotes intestinal epithelial cell migration and reduces the development of necrotizing enterocolitis in a neonatal rat model
复制标题
人β-防御素-3促进新生大鼠模型肠上皮细胞迁移并减少坏死性小肠结肠炎的发展
DOI：
10.1038/pr.2014.93
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发表时间：
2014-09-01
影响因子：
3.6
通讯作者：
Wang, Xueli
中科院分区：
文献类型：
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作者：
Sheng, Qingfeng;Lv, Zhibao;Wang, Xueli
背景技术背景：本研究旨在探讨人β-防御素3（hBD 3）对新生大鼠坏死性小肠结肠炎（NEC）模型肠损伤愈合的影响。评估趋化因子受体CCR 6及其下游信号通路的作用。新生Sprague道利大鼠随机分为4组：对照+NS、对照+hBD 3、NEC+NS和NEC+ hBD 3。体重，组织学评分，生存时间，细胞因子的表达，和粘膜integrity.Results：hBD 3可以刺激肠上皮细胞迁移，但不增殖，无论是在培养的肠上皮细胞和NEC模型。中和抗体和小干扰RNA证实了这种刺激作用是由CCR 6介导的。此外，hBD 3诱导Rho激活，肌球蛋白轻链2磷酸化和F-肌动蛋白积累。hBD 3的杀菌活性在整个宽的pH范围内保持。引人注目的是，hBD 3给药降低了NEC的发生率，增加了存活率，并降低了NEC的严重程度。结论：抗菌肽hBD 3可能通过促进肠上皮细胞迁移参与肠创伤愈合，对NEC新生大鼠具有保护作用。
BACKGROUND: The aim of this study was to investigate the effects of human beta-defensin-3 (hBD3) on intestinal wound healing and in a neonatal rat model of necrotizing enterocolitis (NEC).METHODS: Enterocyte migration and proliferation were detected in vitro and in vivo. The role of chemokine receptor CCR6 and its downstream signaling pathway was assessed. Newborn Sprague Dawley rats were randomly divided into four groups: Control+NS, Control+hBD3, NEC+NS, and NEC+hBD3. Body weight, histological score, survival time, cytokines expression, and mucosal integrity were evaluated.RESULTS: hBD3 could stimulate enterocyte migration, but not proliferation, both in cultured enterocytes and in the NEC model. Neutralizing antibody and small interfering RNA confirmed this stimulatory effect was mediated by CCR6. Furthermore, hBD3 induced Rho activation, myosin light chain 2 phosphorylation, and F-actin accumulation. The bactericidal activity of hBD3 was maintained throughout a broad pH range. Strikingly, hBD3 administration decreased the incidence of NEC, increased the survival rate, and reduced the severity of NEC. Moreover, hBD3 reduced the proinflammatory cytokines expression in ileum and serum and preserved the intestinal barrier integrity.CONCLUSION: This study provided evidence that the antimicrobial peptide hBD3 might participate in intestinal wound healing by promoting enterocyte migration and show beneficial effects on newborn rats with NEC.