title: Intestinal trefoil factor/TFF3 promotes re-epithelialization of corneal wounds.
abstract: 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.
authors.affiliation: Department of Anatomy, Martin Luther University Halle-Wittenberg, D-06097 Halle, Germany. friedrich.paulsen@medizin.uni-halle.de
authors.forename: Friedrich P
authors.initials: FP
authors.lastname: Paulsen
authors.forename: Chee-Wai
authors.initials: CW
authors.lastname: Woon
authors.forename: Deike
authors.initials: D
authors.lastname: Varoga
authors.forename: Anne
authors.initials: A
authors.lastname: Jansen
authors.forename: Fabian
authors.initials: F
authors.lastname: Garreis
authors.forename: Kristin
authors.initials: K
authors.lastname: Jäger
authors.forename: Marita
authors.initials: M
authors.lastname: Amm
authors.forename: Daniel K
authors.initials: DK
authors.lastname: Podolsky
authors.forename: Philipp
authors.initials: P
authors.lastname: Steven
authors.forename: Nicholas P
authors.initials: NP
authors.lastname: Barker
authors.forename: Saadettin
authors.initials: S
authors.lastname: Sel
mesh_terms: 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
chemical_list: D009077:Mucins; D010455:Peptides; D011994:Recombinant Proteins; C082495:TFF3 protein, human; C493263:Tff3 protein, mouse; D000071165:Trefoil Factor-3