Nuclear factor-κB activation promotes restitution of wounded intestinal epithelial monolayers
Nuclear factor-κB activation promotes restitution of wounded intestinal epithelial monolayers
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DOI：
10.1152/ajpcell.00167.2003
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发表时间：
2003-11-01
影响因子：
5.5
通讯作者：
Kagnoff, MF
中科院分区：
文献类型：
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作者：
Egan, LJ;de Lecea, A;Kagnoff, MF
上皮恢复，伤口边缘细胞进入上皮细胞剥脱区域的运动，是溃疡愈合过程中重要的早期步骤。生长因子调节上皮细胞的恢复，但很少有人知道的转录途径介导的细胞迁移的影响。转录因子核因子（NF）-kappaB是宿主炎症反应的主要调节因子，其在肠道炎症的上皮中被激活，这通常伴随上皮损伤。我们推测NF-κ B可能是上皮修复的重要转录调节因子。在非转化大鼠肠上皮（RIE-1）细胞的刮伤单层的体外模型中，NF-κ B在伤口边缘的上皮细胞中被激活。通过药理学或遗传学方法阻断NF-κ B活化抑制肠上皮恢复。此外，刮伤激活表皮生长因子受体（EGFR）在伤口边缘的细胞，重要的是，抑制EGFR酪氨酸激酶活性减少刮伤诱导的NF-κ B活化和细胞迁移。这些结果表明NF-κ B活化在肠上皮细胞恢复和愈合的重要信号通路中的新作用。就NF-κ B在体内可能具有平行功能的程度而言，他们还建议在建议使用NF-κ B抑制剂治疗与肠道和其他粘膜表面的炎症和损伤相关的病症时需要谨慎。
Epithelial restitution, the movement of wound-edge cells into an area of epithelial cell denudation, is an important early step in the ulcer healing process. Growth factors regulate epithelial restitution, yet little is known about the transcriptional pathways that mediate their effects on cell migration. The transcription factor nuclear factor (NF)-kappaB is a master regulator of the host inflammatory response that is activated in the epithelium in intestinal inflammation, which often accompanies epithelial injury. We hypothesized that NF-kappaB may be an important transcriptional regulator of epithelial restitution. In an in vitro model of scrape-wounded monolayers of nontransformed rat intestinal epithelial (RIE-1) cells, NF-kappaB was activated in epithelial cells at the wound edge. Blocking of NF-kappaB activation by either pharmacological or genetic approaches inhibited intestinal epithelial restitution. Moreover, scrape wounding activated the epidermal growth factor receptor (EGFR) in cells at the wound edge, and, importantly, inhibiting EGFR tyrosine kinase activity decreased scrape wound-induced NF-kappaB activation and cell migration. These results indicate a novel role of NF-kappaB activation in a signaling pathway important for restitution and healing of intestinal epithelia. To the extent NF-kappaB may have parallel functions in vivo, they also suggest a need for caution in the proposed use of NF-kappaB inhibitors for the treatment of conditions associated with inflammation and injury of intestinal and other mucosal surfaces.