Beyond epithelial to mesenchymal transition: a novel role for the transcription factor Snail in inflammation and wound healing.
BACKGROUND
Snail, a transcription factor linked to epithelial to mesenchymal transition (EMT) during embryonic development and tumor progression, is associated with migration of cells. During inflammation and tissue injury, cell movement is also observed to provide the first line of defense against bacteria and to promote wound healing. Therefore, we studied the function of Snail in activated macrophages in a variety of inflammatory processes.


METHODS
In this study, we examined the expression and localization of Snail during inflammation and tissue injury in rats and human tissue specimens, by immunohistochemistry, Western blot, and real-time PCR. We investigated Snail expression after stimulation of macrophages with TGF-beta1, LPS, Interleukin-8, and MMP-3 in vitro. To further understand the role of Snail in activated macrophages, we used Stealth siRNA against Snail, transfected the human macrophage cell line THP-1, and measured migration of cells in an in vitro invasion assay.


CONCLUSIONS
We found a strong, transient, and time-dependent activation of Snail in migrating macrophages at the sites of injury in vivo and in vitro, as well as in patients with inflammatory bowel disease. Furthermore, we showed that induction of Snail in macrophages is dependent on TGF-beta1 signaling pathway. Downregulation of Snail by Stealth siRNA led to impaired migration of THP-1 cells in an invasion assay after stimulation with TGF-beta1.


CONCLUSIONS
We conclude that TGF-beta1 induced migration of activated macrophages during inflammation and wound healing is mediated by snail. These results give insights in a novel EMT-like mechanism present in immune cell movement during tissue injury.
Hotz
Birgit
B
Department of Surgery I, Charité School of Medicine, Campus Benjamin Franklin, Hindenburgdamm 30, 12203 Berlin, Germany.
Visekruna
Alexander
A
Buhr
Heinz-Johannes
HJ
Hotz
Hubert Georg
HG
D000818:Animals; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology; D004195:Disease Models, Animal; D006801:Humans; D007249:Inflammation / Q000503:physiopathology*; D008264:Macrophages / Q000187:drug effects*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000494:pharmacology* / Q000502:physiology; D053773:Transforming Growth Factor beta1 / Q000502:physiology; D014945:Wound Healing / Q000187:drug effects*
C000604450:Snai2 protein, rat; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; D053773:Transforming Growth Factor beta1