Department of Microbiology and Institute for Rheumatology Research, Hanyang University College of Medicine, Seoul 04763, Korea.
Int J Mol Sci. 2021 Oct 30;22(21):11817. doi: 10.3390/ijms222111817.
enterotoxin (BFT) produced by enterotoxigenic (ETBF) causes colonic inflammation. BFT initially contacts intestinal epithelial cells (IECs) and affects the intestinal barrier. Although molecular components of the gut epithelial barrier such as metalloproteinase-7 (MMP-7) and syndecan-2 are known to be associated with inflammation, little has been reported about MMP-7 expression and syndecan-2 shedding in response to ETBF infection. This study explores the role of BFT in MMP-7 induction and syndecan-2 release in IECs. Stimulating IECs with BFT led to the induction of MMP-7 and the activation of transcription factors such as NF-κB and AP-1. MMP-7 upregulation was not affected by NF-κB, but it was related to AP-1 activation. In BFT-exposed IECs, syndecan-2 release was observed in a time- and concentration-dependent manner. MMP-7 suppression was associated with a reduction in syndecan-2 release. In addition, suppression of ERK, one of the mitogen-activated protein kinases (MAPKs), inhibited AP-1 activity and MMP-7 expression. Furthermore, the suppression of AP-1 and ERK activity was related to the attenuation of syndecan-2 release. These results suggest that a signaling cascade comprising ERK and AP-1 activation in IECs is involved in MMP-7 upregulation and syndecan-2 release during exposure to BFT.
肠毒素（BFT）由肠毒性（ETBF）产生，导致结肠炎症。BFT 最初与肠上皮细胞（IEC）接触，并影响肠道屏障。尽管肠道上皮屏障的分子成分，如金属蛋白酶-7（MMP-7）和 syndecan-2 与炎症有关，但关于 MMP-7 表达和 syndecan-2 在 ETBF 感染中的脱落知之甚少。本研究探讨了 BFT 在 IEC 中诱导 MMP-7 表达和 syndecan-2 释放中的作用。用 BFT 刺激 IEC 导致 MMP-7 的诱导和转录因子如 NF-κB 和 AP-1 的激活。MMP-7 的上调不受 NF-κB 影响，但与 AP-1 激活有关。在 BFT 暴露的 IEC 中，观察到 syndecan-2 以时间和浓度依赖的方式释放。MMP-7 的抑制与 syndecan-2 释放的减少有关。此外，丝裂原活化蛋白激酶（MAPK）之一 ERK 的抑制抑制了 AP-1 活性和 MMP-7 表达。此外，AP-1 和 ERK 活性的抑制与 syndecan-2 释放的衰减有关。这些结果表明，IEC 中包括 ERK 和 AP-1 激活的信号级联参与了暴露于 BFT 时 MMP-7 的上调和 syndecan-2 的释放。
