Department of Hepatopancreatobiliary Surgery, Second Affiliated Hospital of Harbin Medical University, Harbin, 150086, China.
Mol Biol Rep. 2010 Dec;37(8):3813-8. doi: 10.1007/s11033-010-0036-z. Epub 2010 Mar 13.
Interleukin-6 (IL-6), through activation of the signal transducer and activator of transcription 3 (STAT3) and trefoil factor family 3 (TFF3), has been implicated in the promotion of mouse biliary epithelial cell (BEC) proliferation and migration. However, it is still unclear whether the IL-6/STAT3/TFF3 signaling had similar effects on human BECs. Here, we showed that exposure of human BECs to recombinant IL-6 resulted in STAT3 phosphorylation and increased the expression of TFF3 at both mRNA and protein levels. Moreover, inhibition of STAT3 using RNA interference significantly abrogated IL-6-induced TFF3 expression. In an in-vitro wound healing model, IL-6 facilitated human BEC migration. This promotion of cell migration by IL-6 was blocked when STAT3 was knocked down. Interestingly, the addition of exogenous TFF3 could rescue the cell migration defects caused by STAT3 silencing. In conclusion, our data indicate that STAT3 plays a critical role in IL-6-induced TFF3 expression in human BECs and the IL-6/STAT3/TFF3 signaling is involved in human BEC migration and wound healing.
白细胞介素 6（IL-6）通过激活信号转导子和转录激活子 3（STAT3）和三叶因子家族 3（TFF3），被认为促进了小鼠胆管上皮细胞（BEC）的增殖和迁移。然而，目前尚不清楚 IL-6/STAT3/TFF3 信号是否对人 BEC 具有相似的作用。在这里，我们表明，重组 IL-6 暴露于人 BEC 中会导致 STAT3 磷酸化，并增加 TFF3 在 mRNA 和蛋白质水平上的表达。此外，使用 RNA 干扰抑制 STAT3 显著阻断了 IL-6 诱导的 TFF3 表达。在体外划痕愈合模型中，IL-6 促进人 BEC 的迁移。当 STAT3 被敲低时，这种细胞迁移的促进作用被阻断。有趣的是，添加外源性 TFF3 可以挽救由 STAT3 沉默引起的细胞迁移缺陷。总之，我们的数据表明 STAT3 在 IL-6 诱导的人 BEC 中 TFF3 表达中起关键作用，IL-6/STAT3/TFF3 信号参与人 BEC 迁移和伤口愈合。
