Intestinal trefoil factor/TFF3 promotes re-epithelialization of corneal wounds

Friedrich P. Paulsen, Chee Wai Woon, Deike Varoga, Anne Jansen, Fabian Garreis, Kristin Jäger, Marita Amm, Daniel K. Podolsky, Philipp Steven, Nicholas P. Barker, Saadettin Sel

Research output: Contribution to journalArticle

45 Citations (Scopus)

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 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.

Original languageEnglish (US)
Pages (from-to)13418-13427
Number of pages10
JournalJournal of Biological Chemistry
Volume283
Issue number19
DOIs
StatePublished - May 9 2008

Fingerprint

Re-Epithelialization
Wound Healing
Wounds and Injuries
Alkalies
Cornea
Peptides
Medical problems
Corneal Epithelium
Tissue
Trefoil Factor-3
Lasers

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Paulsen, F. P., Woon, C. W., Varoga, D., Jansen, A., Garreis, F., Jäger, K., ... Sel, S. (2008). Intestinal trefoil factor/TFF3 promotes re-epithelialization of corneal wounds. Journal of Biological Chemistry, 283(19), 13418-13427. https://doi.org/10.1074/jbc.M800177200

Intestinal trefoil factor/TFF3 promotes re-epithelialization of corneal wounds. / Paulsen, Friedrich P.; Woon, Chee Wai; Varoga, Deike; Jansen, Anne; Garreis, Fabian; Jäger, Kristin; Amm, Marita; Podolsky, Daniel K.; Steven, Philipp; Barker, Nicholas P.; Sel, Saadettin.

In: Journal of Biological Chemistry, Vol. 283, No. 19, 09.05.2008, p. 13418-13427.

Research output: Contribution to journalArticle

Paulsen, FP, Woon, CW, Varoga, D, Jansen, A, Garreis, F, Jäger, K, Amm, M, Podolsky, DK, Steven, P, Barker, NP & Sel, S 2008, 'Intestinal trefoil factor/TFF3 promotes re-epithelialization of corneal wounds', Journal of Biological Chemistry, vol. 283, no. 19, pp. 13418-13427. https://doi.org/10.1074/jbc.M800177200
Paulsen FP, Woon CW, Varoga D, Jansen A, Garreis F, Jäger K et al. Intestinal trefoil factor/TFF3 promotes re-epithelialization of corneal wounds. Journal of Biological Chemistry. 2008 May 9;283(19):13418-13427. https://doi.org/10.1074/jbc.M800177200
Paulsen, Friedrich P. ; Woon, Chee Wai ; Varoga, Deike ; Jansen, Anne ; Garreis, Fabian ; Jäger, Kristin ; Amm, Marita ; Podolsky, Daniel K. ; Steven, Philipp ; Barker, Nicholas P. ; Sel, Saadettin. / Intestinal trefoil factor/TFF3 promotes re-epithelialization of corneal wounds. In: Journal of Biological Chemistry. 2008 ; Vol. 283, No. 19. pp. 13418-13427.
@article{f90cdb59dff148ae8cf1e6d4ba5f43ed,
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 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.",
author = "Paulsen, {Friedrich P.} and Woon, {Chee Wai} and Deike Varoga and Anne Jansen and Fabian Garreis and Kristin J{\"a}ger and Marita Amm and Podolsky, {Daniel K.} and Philipp Steven and Barker, {Nicholas P.} and Saadettin Sel",
year = "2008",
month = "5",
day = "9",
doi = "10.1074/jbc.M800177200",
language = "English (US)",
volume = "283",
pages = "13418--13427",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "19",

}

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.

UR - http://www.scopus.com/inward/record.url?scp=45149097431&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=45149097431&partnerID=8YFLogxK

U2 - 10.1074/jbc.M800177200

DO - 10.1074/jbc.M800177200

M3 - Article

C2 - 18326859

AN - SCOPUS:45149097431

VL - 283

SP - 13418

EP - 13427

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

IS - 19

ER -