Esophageal ulceration activates keratinocyte growth factor and its receptor in rats: implications for ulcer healing.

Abstract:

BACKGROUND & AIMS: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.

journal_name

Gastroenterology

journal_title

Gastroenterology

authors

Baatar D,Kawanaka H,Szabo IL,Pai R,Jones MK,Kitano S,Tarnawski AS

doi

10.1053/gast.2002.31004

keywords:

subject

Has Abstract

pub_date

2002-02-01 00:00:00

pages

458-68

issue

2

eissn

0016-5085

issn

1528-0012

pii

S0016508502444551

journal_volume

122

pub_type

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