Intestinal trefoil factor/TFF3 promotes re-epithelialization of corneal wounds.
Disorders of wound healing characterized by impaired or delayed re-epithelialization are a serious medical problem. These conditions affect many tissues, are painful, and are difficult to treat. In this study using cornea as a model, we demonstrate the importance of trefoil factor 3 (TFF3, also known as intestinal trefoil factor) in re-epithelialization of wounds. In two different models of corneal wound healing, alkali- and laser-induced corneal wounding, we analyzed the wound healing process in in vivo as well as in combined in vivo/in vitro model in wild type (Tff3(+)(/)(+)) and Tff3-deficient (Tff3(-)(/)(-)) mice. Furthermore, we topically applied different concentrations of recombinant human TFF3 (rTFF3) peptide on the wounded cornea to determine the efficacy of rTFF3 on corneal wound healing. We found that Tff3 peptide is not expressed in intact corneal epithelium, but its expression is extensively up-regulated after epithelial injury. Re-epithelialization of corneal wounds in Tff3(-/-) mice is significantly prolonged in comparison to Tff3(+/+) mice. In addition, exogenous application of rTFF3 to the alkali-induced corneal wounds accelerates significantly in in vivo and in combined in vivo/in vitro model wound healing in Tff3(+/+) and Tff3(-/-) mice. These findings reveal a pivotal role for Tff3 in corneal wound healing mechanism and have broad implications for developing novel therapeutic strategies for treating nonhealing wounds.
Paulsen
Friedrich P
FP
Department of Anatomy, Martin Luther University Halle-Wittenberg, D-06097 Halle, Germany. friedrich.paulsen@medizin.uni-halle.de
Woon
Chee-Wai
CW
Varoga
Deike
D
Jansen
Anne
A
Garreis
Fabian
F
Jäger
Kristin
K
Amm
Marita
M
Podolsky
Daniel K
DK
Steven
Philipp
P
Barker
Nicholas P
NP
Sel
Saadettin
S
D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D048430:Cell Shape; D003315:Cornea / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D065306:Corneal Injuries; D004195:Disease Models, Animal; D004847:Epithelial Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D008855:Microscopy, Electron, Scanning; D009077:Mucins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D010455:Peptides / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000494:pharmacology; D014158:Transcription, Genetic / Q000235:genetics; D000071165:Trefoil Factor-3; D014945:Wound Healing / Q000187:drug effects
D009077:Mucins; D010455:Peptides; D011994:Recombinant Proteins; C082495:TFF3 protein, human; C493263:Tff3 protein, mouse; D000071165:Trefoil Factor-3