IL-6/STAT3/TFF3 signaling regulates human biliary epithelial cell migration and wound healing in vitro.
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.
Department of Hepatopancreatobiliary Surgery, Second Affiliated Hospital of Harbin Medical University, Harbin, 150086, China.
Gui-xing
GX
Jiang
Xiang-yu
XY
Zhong
Yun-fu
YF
Cui
Wei
W
Liu
Sheng
S
Tai
Zhi-dong
ZD
Wang
Yu-guang
YG
Shi
Shi-yong
SY
Zhao
Chun-long
CL
Li
D000818:Animals; D001659:Biliary Tract / Q000473:pathology; D001681:Biological Assay; D002465:Cell Movement; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology*; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism*; D051379:Mice; D010455:Peptides / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D034622:RNA Interference; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction; D000071165:Trefoil Factor-3; D014945:Wound Healing
C508600:IL6 protein, human; D015850:Interleukin-6; D010455:Peptides; D012333:RNA, Messenger; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; C082495:TFF3 protein, human; D000071165:Trefoil Factor-3