Integrative roles of transforming growth factor-α in the cytoprotection mechanisms of gastric mucosal injuryReport as inadecuate

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BMC Gastroenterology

, 6:22

First Online: 01 August 2006Received: 22 December 2005Accepted: 01 August 2006


BackgroundTransforming 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.

MethodsTGFα-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.

ResultsIn 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.

ConclusionWe conclude that TGFα maintains the gastric mucosal defense against gastric injury by integrating other cytoprotective mechanisms.

AbbreviationsTGFαtransforming growth factor α



EGF-Repidermal growth factor receptor

COXcyclooxygenase: NOS, nitric oxide synthase

HSPheat shock protein

GSMgastric surface mucosa

HRPhorseradish peroxydase

Electronic supplementary materialThe online version of this article doi:10.1186-1471-230X-6-22 contains supplementary material, which is available to authorized users.

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Author: Takashi Kosone - Hitoshi Takagi - Satoru Kakizaki - Naondo Sohara - Norio Horiguchi - Ken Sato - Masashi Yoneda - Toshiyuki


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