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      헬리코박터 파일로리 감염 연관 위질환 발생시 형질전환인자-베타 저해신호로서 Smad7의 역할 = Role of Inhibitory Transforming Growth Factor-β Signal Smad7 in Helicobacter pylori-associated Gastric Damage

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      https://www.riss.kr/link?id=A102133048

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      다국어 초록 (Multilingual Abstract)

      Background/Aims: Transforming growth factor-beta (TGF-β) is a cytokine implicated in the susceptibility, development, and pro-gression of gastrointestinal cancer and certain other neoplasms. In the later stages of cancer, TGF-β not only acts as a bystander of host-immune response, but also contributes to cell growth, invasion, and metastasis. In the current study, we generated gastric mucosal cells that stably express Smad7, and explored the Helicobacter pylori-associated biological changes between mock-transfected and Smad7-transfected RGM1 cells. Methods: RGM1 cells stably transfected with Smad7 were infected with H. pylori, and molecular changes in apoptotic markers and inflammatory mediators were examined. Several candidate genes were explored in Smad7-overexpressing cells after H. pylori infection. Results: Overexpression of Smad7 in RGM1 cells significantly increased the H. pylori-induced cytotoxicity compared to mock-trans-fected cells. Exaggerated increases in inflammatory mediators, cyclooxygenase 2, inducible NO synthase, and augmented apoptosis were noted in Smad7-overexpressing cells, whereas mitigated heme oxygenase 1 was noted in Smad7- overexpressing cells. These phenomena were reversed in cells transfected with Smad7 siRNA. Conclusions: These data suggest that inhibition of Smad7 is a possible target for mitigating H. pylori-associated inflammation. (Korean J Gastroenterol 2016;68:186-194)
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      Background/Aims: Transforming growth factor-beta (TGF-β) is a cytokine implicated in the susceptibility, development, and pro-gression of gastrointestinal cancer and certain other neoplasms. In the later stages of cancer, TGF-β not only acts as a by...

      Background/Aims: Transforming growth factor-beta (TGF-β) is a cytokine implicated in the susceptibility, development, and pro-gression of gastrointestinal cancer and certain other neoplasms. In the later stages of cancer, TGF-β not only acts as a bystander of host-immune response, but also contributes to cell growth, invasion, and metastasis. In the current study, we generated gastric mucosal cells that stably express Smad7, and explored the Helicobacter pylori-associated biological changes between mock-transfected and Smad7-transfected RGM1 cells. Methods: RGM1 cells stably transfected with Smad7 were infected with H. pylori, and molecular changes in apoptotic markers and inflammatory mediators were examined. Several candidate genes were explored in Smad7-overexpressing cells after H. pylori infection. Results: Overexpression of Smad7 in RGM1 cells significantly increased the H. pylori-induced cytotoxicity compared to mock-trans-fected cells. Exaggerated increases in inflammatory mediators, cyclooxygenase 2, inducible NO synthase, and augmented apoptosis were noted in Smad7-overexpressing cells, whereas mitigated heme oxygenase 1 was noted in Smad7- overexpressing cells. These phenomena were reversed in cells transfected with Smad7 siRNA. Conclusions: These data suggest that inhibition of Smad7 is a possible target for mitigating H. pylori-associated inflammation. (Korean J Gastroenterol 2016;68:186-194)

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      참고문헌 (Reference)

      1 Pickup M, "The roles of TGF in the tumour microenvironment" 13 : 788-799, 2013

      2 Akhurst RJ, "Targeting the TGF signalling pathway in disease" 11 : 790-811, 2012

      3 Schmierer B, "TGFbeta-SMAD signal transduction: molecular specificity and functional flexibility" 8 : 970-982, 2007

      4 Ikushima H, "TGFbeta signalling: a complex web in cancer progression" 10 : 415-424, 2010

      5 Monteleone G, "TGF-beta1and Smad7 in the regulation of IBD" 1 (1): S50-S53, 2008

      6 조윤정, "Suppressed Gastric Mucosal TGF-β1 Increases Susceptibility to H. pylori-Induced Gastric Inflammation and Ulceration: A Stupid Host Defense Response" 거트앤리버 발행위원회 4 (4): 43-53, 2010

      7 Shiotani A, "Sonic hedgehog and CDX2 expression in the stomach" 23 (23): S161-S166, 2008

      8 Yan X, "Smad7: not only a regulator, but also a cross-talk mediator of TGF-signalling" 434 : 1-10, 2011

      9 Monteleone G, "Smad7 in TGF-beta-mediated negative regulation of gut inflammation" 25 : 513-517, 2004

      10 Hong S, "Smad7 binds to the adaptors TAB2and TAB3 to block recruitment of the kinase TAK1 to the adaptor TRAF2" 8 : 504-513, 2007

      1 Pickup M, "The roles of TGF in the tumour microenvironment" 13 : 788-799, 2013

      2 Akhurst RJ, "Targeting the TGF signalling pathway in disease" 11 : 790-811, 2012

      3 Schmierer B, "TGFbeta-SMAD signal transduction: molecular specificity and functional flexibility" 8 : 970-982, 2007

      4 Ikushima H, "TGFbeta signalling: a complex web in cancer progression" 10 : 415-424, 2010

      5 Monteleone G, "TGF-beta1and Smad7 in the regulation of IBD" 1 (1): S50-S53, 2008

      6 조윤정, "Suppressed Gastric Mucosal TGF-β1 Increases Susceptibility to H. pylori-Induced Gastric Inflammation and Ulceration: A Stupid Host Defense Response" 거트앤리버 발행위원회 4 (4): 43-53, 2010

      7 Shiotani A, "Sonic hedgehog and CDX2 expression in the stomach" 23 (23): S161-S166, 2008

      8 Yan X, "Smad7: not only a regulator, but also a cross-talk mediator of TGF-signalling" 434 : 1-10, 2011

      9 Monteleone G, "Smad7 in TGF-beta-mediated negative regulation of gut inflammation" 25 : 513-517, 2004

      10 Hong S, "Smad7 binds to the adaptors TAB2and TAB3 to block recruitment of the kinase TAK1 to the adaptor TRAF2" 8 : 504-513, 2007

      11 Wang W, "Signaling mechanism of TGF-beta1in prevention of renal inflammation: role of Smad7" 16 : 1371-1383, 2005

      12 Beswick EJ, "Role of gastric epithelial cell-derived transforming growth factor beta in reduced CD4+ T cell proliferation and development of regulatory T cells during Helicobacter pylori infection" 79 : 2737-2745, 2011

      13 Monteleone G, "Role of Smad7 in inflammatory bowel diseases" 18 : 5664-5668, 2012

      14 Hahm KB, "Repression of the gene encoding the TGF-beta type II receptor is a major target of the EWS-FLI1oncoprotein" 23 : 222-227, 1999

      15 Nguyen TT, "Repressed TGF-signaling through CagA-Smad3 interaction as pathogenic mechanisms of Helicobacter pylori-associated gastritis" 57 : 113-120, 2015

      16 Tsugawa H, "Reactive oxygen species-induced autophagic degradation of Helicobacter pylori CagA is specifically suppressed in cancer stem-like cells" 12 : 764-777, 2012

      17 Han G, "Preventive and therapeutic effects of Smad7 on radiation-induced oral mucositis" 19 : 421-428, 2013

      18 Ardizzone S, "Mongersen, an oral Smad7 antisense oligonucleotide, in patients with active Crohn's disease" 9 : 527-532, 2016

      19 Monteleone G, "Mongersen, an oral SMAD7 antisense oligonucleotide, and Crohn's disease" 372 : 1104-1113, 2015

      20 Hahm KB, "Loss of transforming growth factor beta signalling in the intestine contributes to tissue injury in inflammatory bowel disease" 49 : 190-198, 2001

      21 Hahm KB, "Loss of TGF-beta signaling contributes to autoimmune pancreatitis" 105 : 1057-1065, 2000

      22 Lee KM, "Late reactivation of sonic hedgehog by Helicobacter pylori results in population of gastric epithelial cells that are resistant to apoptosis:implication for gastric carcinogenesis" 287 : 44-53, 2010

      23 Yang YJ, "Lactobacillus acidophilus ameliorates H. pylori-induced gastric inflammation by inactivating the Smad7 and NFκB pathways" 12 : 38-, 2012

      24 Barros R, "Key elements of the BMP/SMAD pathway co-localize with CDX2 in intestinal metaplasia and regulate CDX2 expression in human gastric cell lines" 215 : 411-420, 2008

      25 Boirivant M, "Inhibition of Smad7with a specific antisense oligonucleotide facilitates TGF-beta1-mediated suppression of colitis" 131 : 1786-1798, 2006

      26 Monteleone G, "Induction and regulation of Smad7 in the gastric mucosa of patients with Helicobacter pylori infection" 126 : 674-682, 2004

      27 Monteleone G, "Impact of patient characteristics on the clinical efficacy of mongersen (GED-0301), an oral Smad7 antisense oligonucleotide, in activeCrohn's disease" 43 : 717-724, 2016

      28 Datta De D, "IL1B induced Smad 7 negatively regulates gastrin expression" 6 : e14775-, 2011

      29 Im YH, "Heterozygous mice for the transforming growth factor-beta type II receptor gene have increased susceptibility to hepatocellular carcinogenesis" 61 : 6665-6668, 2001

      30 Han SU, "Helicobacter pylori infection promotes gastric carcinogenesis in a mice model" 17 : 253-261, 2002

      31 Camilo V, "Helicobacter pylori and the BMP pathway regulate CDX2 and SOX2 expression in gastric cells" 33 : 1985-1992, 2012

      32 Akazawa Y, "Endoplasmic reticulum stress contributes to Helicobacter pylori VacA-induced apoptosis" 8 : e82322-, 2013

      33 Yingling JM, "Development of TGF-beta signalling inhibitors for cancer therapy" 3 : 1011-1022, 2004

      34 Siegel PM, "Cytostatic and apoptotic actions of TGF-beta in homeostasis and cancer" 3 : 807-821, 2003

      35 Yuasa Y, "Control of gut differentiation and intestinal-type gastric carcinogenesis" 3 : 592-600, 2003

      36 Hahm KB, "Conditional loss of TGF-beta signalling leads to increased susceptibility to gastrointestinal carcinogenesis in mice" 16 (16): 115-127, 2002

      37 Monteleone G, "Blocking Smad7 restores TGF-beta1 signaling in chronic inflammatory bowel disease" 108 : 601-609, 2001

      38 Wakefield LM, "Beyond TGF: roles of other TGF superfamily members in cancer" 13 : 328-341, 2013

      39 Park S, "Amelioration of oxidative stress with ensuing inflammation contributes to chemoprevention of H. pylori-associated gastric carcinogenesis" 6 : 549-560, 2004

      40 Monteleone G, "A failure of transforming growth factor-beta1 negative regulation maintains sustained NF-kappaB activation in gut inflammation" 279 : 3925-3932, 2004

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      학술지 이력
      연월일 이력구분 이력상세 등재구분
      2022 평가예정 재인증평가 신청대상 (재인증)
      2019-01-01 평가 등재학술지 유지 (계속평가) KCI등재
      2011-01-01 평가 등재학술지 유지 (등재유지) KCI등재
      2009-01-01 평가 등재학술지 유지 (등재유지) KCI등재
      2007-01-01 평가 등재학술지 유지 (등재유지) KCI등재
      2005-01-01 평가 등재학술지 유지 (등재유지) KCI등재
      2002-01-01 평가 등재학술지 선정 (등재후보2차) KCI등재
      1999-07-01 평가 등재후보학술지 선정 (신규평가) KCI등재후보
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      기준연도 WOS-KCI 통합IF(2년) KCIF(2년) KCIF(3년)
      2016 0.18 0.18 0.18
      KCIF(4년) KCIF(5년) 중심성지수(3년) 즉시성지수
      0.21 0.2 0.315 0.03
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