| セッション情報 |
The 4th International Forum
Best Short Oral Presentations（GI mucosal injury）
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| タイトル |
IFI-BSOP-2：Role of the TGF-β signaling inhibitor Smad7 in NSAIDs-induced gastric mucosal damage
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| 演者 |
Kwon Sung-Hun（CHA Cancer Prevention Research Center, CHA Cancer Institute, CHA University, Korea） |
| 共同演者 |
Park Jong-Min（CHA Cancer Prevention Research Center, CHA Cancer Institute, CHA University, Korea）, Kim Eun-Hee（CHA Cancer Prevention Research Center, CHA Cancer Institute, CHA University, Korea）, Park Pil-Won（Department of Gastroenterology, CHA Bundang Medical Center, Korea）, Hong Sung-Pyo（Department of Gastroenterology, CHA Bundang Medical Center, Korea）, Ko Kwang-Hyun（Department of Gastroenterology, CHA Bundang Medical Center, Korea）, Hahm Ki-Baik（CHA Cancer Prevention Research Center, CHA Cancer Institute, CHA University, KoreaDELIMITERDepartment of Gastroenterology, CHA Bundang Medical Center, Korea） |
| 抄録 |
BACKGROUND ＆ AIMs：Smad7 has been generally regarded as inhibitory signaling of transforming growth factor（TGF）-β superfamily, thereby blocking TGF-β-induced cell proliferation, apoptosis, and inflammation in gastric cells. Inflammation, apoptosis, endoplasmic reticulum-stress, and autophagic cell death have been identified as key cytotoxic mechanisms implicated in NSAIDs-induced gastric damage. Therefore, we hypothesized whether Smad7 can alleviate NSAID-induced gastritis.
METHODS：To investigate the biological role of TGF-β1 or its antagonist, Smad7, in NSAIDs-induced gastric damage, respectively, we generated Smad7 overexpressed RGM1 cells. Using these cells, we compared the different gene expression between normal cells and overexpressed-Smad7 cells after NSAIDs treatment by high throughput analysis of cDNA microarray. We validated the findings by detecting the protein expression of inflammation-, proliferation-, apoptosis-, and autophagy-related mediators.
RESULTS：We found that Smad7 plays pivotal roles in NSAIDs-induced inflammation, apoptosis, and especially autophagic cell death. Smad7 overexpression suppressed indomethacin-induced apoptosis and autophagic cell death, quite contrary implications of Smad7 according to kind of irritants. Interestingly, indomathacin treatment decreased the expression of Smad7 and induced gastric damage by Smad7 degradation as confirmed by Smad7 knockdown.
CONCLUSIONS：Our novel findings suggest that the maintenance of Smad7 expression may have therapeutic actions in NSAIDs-induced gastric injury, via inhibition of apoptosis and autophagy in gastric damages. |
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