TY - JOUR
T1 - Intestinal trefoil factor/TFF3 promotes re-epithelialization of corneal wounds
AU - Paulsen, Friedrich P.
AU - Woon, Chee Wai
AU - Varoga, Deike
AU - Jansen, Anne
AU - Garreis, Fabian
AU - Jäger, Kristin
AU - Amm, Marita
AU - Podolsky, Daniel K.
AU - Steven, Philipp
AU - Barker, Nicholas P.
AU - Sel, Saadettin
PY - 2008/5/9
Y1 - 2008/5/9
N2 - 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 invivo and incombined in vivo/in vitro model wound healing in Tff3+/+ and Tff3Tff3 -/- 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.
AB - 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 invivo and incombined in vivo/in vitro model wound healing in Tff3+/+ and Tff3Tff3 -/- 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.
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U2 - 10.1074/jbc.M800177200
DO - 10.1074/jbc.M800177200
M3 - Article
C2 - 18326859
AN - SCOPUS:45149097431
SN - 0021-9258
VL - 283
SP - 13418
EP - 13427
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 19
ER -