Saccharomyces boulardii Improves Intestinal Cell Restitution through Activation of the α2β1 Integrin Collagen Receptor
Saccharomyces boulardii Improves Intestinal Cell Restitution through Activation of the α2β1 Integrin Collagen Receptor
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DOI：
10.1371/journal.pone.0018427
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发表时间：
2011-03-31
期刊：
影响因子：
3.7
通讯作者：
Andre, Frederic
中科院分区：
文献类型：
--
作者：
Canonici, Alexandra;Siret, Carole;Andre, Frederic
肠上皮细胞损伤常见于炎性肠病如溃疡性结肠炎或克罗恩病的粘膜病变中。这些疾病的完全缓解需要炎症的停止和肠上皮细胞的迁移以修复受损的上皮。冻干布拉酵母菌（Sb，Biocodex）是一种非致病性酵母菌，广泛用作治疗剂，用于治疗和预防腹泻和其他胃肠道疾病。在这项研究中，我们确定锑是否可以加速肠上皮细胞迁移。在Sb强制喂食的C57 BL 6 J小鼠和体外伤口模型中测定细胞迁移。使用粘附试验和体外和体内α 2 β 1介导的信号通路分析评估对α 2 β 1整联蛋白活性的影响。我们证明，锑分泌的化合物，增强独立于细胞增殖的肠上皮细胞的迁移。这种增强的迁移与Sb有利于细胞-细胞外基质相互作用的能力有关。事实上，酵母激活α 2 β 1整合素胶原蛋白受体。这导致细胞质分子的酪氨酸磷酸化增加，包括粘着斑激酶和桩蛋白，参与整联蛋白信号传导途径。这些变化与粘着斑结构的重组有关。总之，锑分泌运动因子，通过动态调节α 2 β 1整合素活性增强细胞恢复。这对于开发针对以严重粘膜损伤为特征的疾病（如炎症性和感染性肠病）的新疗法具有重要意义。
Intestinal epithelial cell damage is frequently seen in the mucosal lesions of inflammatory bowel diseases such as ulcerative colitis or Crohn's disease. Complete remission of these diseases requires both the cessation of inflammation and the migration of enterocytes to repair the damaged epithelium. Lyophilized Saccharomyces boulardii (Sb, Biocodex) is a nonpathogenic yeast widely used as a therapeutic agent for the treatment and prevention of diarrhea and other gastrointestinal disorders. In this study, we determined whether Sb could accelerate enterocyte migration. Cell migration was determined in Sb force-fed C57BL6J mice and in an in vitro wound model. The impact on alpha 2 beta 1 integrin activity was assessed using adhesion assays and the analysis of alpha 2 beta 1 mediated signaling pathways both in vitro and in vivo. We demonstrated that Sb secretes compounds that enhance the migration of enterocytes independently of cell proliferation. This enhanced migration was associated with the ability of Sb to favor cell-extracellular matrix interaction. Indeed, the yeast activates alpha 2 beta 1 integrin collagen receptors. This leads to an increase in tyrosine phosphorylation of cytoplasmic molecules, including focal adhesion kinase and paxillin, involved in the integrin signaling pathway. These changes are associated with the reorganization of focal adhesion structures. In conclusion Sb secretes motogenic factors that enhance cell restitution through the dynamic regulation of alpha 2 beta 1 integrin activity. This could be of major importance in the development of novel therapies targeting diseases characterized by severe mucosal injury, such as inflammatory and infectious bowel diseases.