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Integrative roles of transforming growth factor-α in the cytoprotection mechanisms of gastric mucosal injury

Integrative roles of transforming growth factor-α in the cytoprotection mechanisms of gastric mucosal injury

Authors :
Yoneda Masashi
Sato Ken
Horiguchi Norio
Sohara Naondo
Kakizaki Satoru
Takagi Hitoshi
Kosone Takashi
Takeuchi Toshiyuki
Mori Masatomo
Source :
BMC Gastroenterology, Vol 6, Iss 1, p 22 (2006)
Publication Year :
2006
Publisher :
BMC, 2006.

Abstract

Abstract Background Transforming growth factor α (TGFα) protects against gastric mucosal injury and facilitates wound healing. However, its overexpression is known to induce hypertrophic gastropathy resembling Menetrier's disease in transgenic (TG) mice on an FVB background, as one of the authors reported previously. We studied another TGFα-expressing mouse line on a CD1 background, whose gastric mucosa appears normal. Since this TG mouse had a strong resistance to ethanol-induced gastric injury, we considered the long-term effect of TGFα on several gastric protection mechanisms. Methods TGFα-expressing transgenic (TG) mouse lines bearing human TGFα cDNA under the control of the mouse metallothionein gene I promoter were generated on a CD1 mouse background, and analyzed their ethanol injury-resistant phenotypes produced by TGFα. Results In the TG mucosa, blood flow was well maintained after ethanol injury. Further, neural and inducible types of NO synthases were consistently and widely expressed in the TG mucosa, compared with the limited distribution of neural type NO synthase in the luminal pit region of the wild-type (WT) mucosa. COX-2 and its upstream transcription factor NfkB were constitutively elevated in the TG mucosa even before ethanol administration, whereas they were induced in the same region of the WT mucosa only after ethanol injury. Two anti-apoptotic proteins, HSP70 and Bcl-2, were upregulated in the TG mucosa even before ethanol administration, while they were not expressed in the WT mucosa before the injury. Furthermore, pro-caspase 3 activation was inhibited in the TG mucosa, while it was converted to the active form in the WT mucosa following ethanol administration. Conclusion We conclude that TGFα maintains the gastric mucosal defense against gastric injury by integrating other cytoprotective mechanisms.

Details

Language :
English
ISSN :
1471230X
Volume :
6
Issue :
1
Database :
Directory of Open Access Journals
Journal :
BMC Gastroenterology
Publication Type :
Academic Journal
Accession number :
edsdoj.39ec9a20babc4f26ae1d7e04de94db6a
Document Type :
article
Full Text :
https://doi.org/10.1186/1471-230X-6-22