Trefoil peptides promote restitution of wounded corneal epithelial cells.
The ocular surface shares many characteristics with mucosal surfaces. In both, healing is regulated by peptide growth factors, cytokines, and extracellular matrix proteins. However, these factors are not sufficient to ensure most rapid healing. Trefoil peptides are abundantly expressed epithelial cell products which exert protective effects and are key regulators of gastrointestinal epithelial restitution, the critical early phase of cell migration after mucosal injury. To assess the role of trefoil peptides in corneal epithelial wound healing, the effects of intestinal trefoil factor (ITF/TFF3) and spasmolytic polypeptide (SP/TFF2) on migration and proliferation of corneal epithelial cells were analyzed. Both ITF and SP enhanced restitution of primary rabbit corneal epithelial cells in vitro. While the restitution-enhancing effects of TGF-alpha and TGF-beta were both inhibited by neutralizing anti-TGF-beta-antibodies, trefoil peptide stimulation of restitution was not. Neither trefoil peptide significantly affected proliferation of primary corneal epithelial cells. ITF but not SP or pS2 mRNA was present in rabbit corneal and conjunctival tissues. In summary, the data indicate an unanticipated role of trefoil peptides in healing of ocular surface and demand rating their functional actions beyond the gastrointestinal tract.
Gastrointestinal Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, USA.
M N
MN
Göke
J R
JR
Cook
K S
KS
Kunert
M E
ME
Fini
I K
IK
Gipson
D K
DK
Podolsky
D000818:Animals; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects; D019573:Epithelium, Corneal / Q000166:cytology / Q000502:physiology*; D015870:Gene Expression; D006133:Growth Substances / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D006801:Humans; D009077:Mucins; D009124:Muscle Proteins; D009479:Neuropeptides; D010455:Peptides / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D011506:Proteins / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D012333:RNA, Messenger; D011817:Rabbits; D016211:Transforming Growth Factor alpha / Q000494:pharmacology; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D053773:Transforming Growth Factor beta1; D000071164:Trefoil Factor-2; D000071165:Trefoil Factor-3; D014945:Wound Healing / Q000502:physiology*
D006133:Growth Substances; D009077:Mucins; D009124:Muscle Proteins; D009479:Neuropeptides; D010455:Peptides; D011506:Proteins; D012333:RNA, Messenger; C000604007:TFF2 protein, human; C082495:TFF3 protein, human; C099037:TFF3 protein, rat; C508960:TGFB1 protein, human; C000604008:Tff2 protein, rat; C508962:Tgfb1 protein, rat; D016211:Transforming Growth Factor alpha; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D000071164:Trefoil Factor-2; D000071165:Trefoil Factor-3