Esophageal ulceration activates keratinocyte growth factor and its receptor in rats: implications for ulcer healing.
OBJECTIVE
Cellular and molecular mechanisms of esophageal ulcer healing remain unexplored. We studied the sequential cellular events and the expression of keratinocyte growth factor (KGF) and its receptor (KGF-R) during the healing of experimental esophageal ulcers.


METHODS
Esophageal ulcers were produced in rats by local application of acetic acid. Studies included (1) ulcer size, (2) quantitative histology, and (3) KGF and KGF-R messenger RNA and protein expression by reverse-transcription polymerase chain reaction, Western blotting, and immunostaining. In separate groups, ulcer size and esophageal epithelial proliferation were evaluated after a single injection of recombinant human KGF (1 mg/kg) around the ulcer.


RESULTS
Ulcers were fully developed 3 days after induction, and 58% of ulcers were re-epithelialized by 9 days. At 3 days, in esophageal tissue bordering the ulcers, KGF messenger RNA and protein were increased by 191% and 151%, respectively, and KGF-R messenger RNA and protein were increased by 357% and 237%, respectively. KGF was expressed in stromal cells, whereas KGF-R was expressed in epithelial cells. At 6 days, epithelial proliferation at the ulcer margin was increased by 216%, and treatment with KGF further enhanced cell proliferation and accelerated ulcer healing.


CONCLUSIONS
KGF is a likely mediator of esophageal epithelial proliferation and ulcer healing.
Baatar
Dolgor
D
Department of Veterans Affairs Medical Center, Long Beach, California 90822, USA.
Kawanaka
Hirofumi
H
Szabo
Imre L
IL
Pai
Rama
R
Jones
Michael K
MK
Kitano
Seigo
S
Tarnawski
Andrzej S
AS
D000818:Animals; D015153:Blotting, Western; D002455:Cell Division / Q000187:drug effects; D004847:Epithelial Cells / Q000166:cytology / Q000502:physiology; D004935:Esophageal Diseases / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D051523:Fibroblast Growth Factor 7; D005346:Fibroblast Growth Factors / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D005455:Fluorescent Antibody Technique; D015870:Gene Expression / Q000502:physiology; D008297:Male; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D051497:Receptor, Fibroblast Growth Factor, Type 2; D017468:Receptors, Fibroblast Growth Factor / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014456:Ulcer / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D014945:Wound Healing / Q000187:drug effects / Q000502:physiology*
C496455:Fgf7 protein, rat; D012333:RNA, Messenger; D017468:Receptors, Fibroblast Growth Factor; D051523:Fibroblast Growth Factor 7; D005346:Fibroblast Growth Factors; D051497:Receptor, Fibroblast Growth Factor, Type 2; C065104:keratinocyte growth factor receptor