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Epigallocatechin-3-gallate suppresses transforming growth factor-beta signaling by interacting with the transforming growth factor-beta typeⅡreceptor

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World Journal of Experimental Medicine 2013年第4期3卷 100-107页

作者： Masaki Tabuchi sumio hayakawa Eiko Honda Kana Ooshima Tatsuki Itoh Koji Yoshida Ah-Mee Park Hideaki Higashino Mamoru Isemura Hiroshi Munakata Department of Biochemistry Kinki University Faculty of Medicine Division of Signaling in Cancer and Immunology Institute for Genetic Medicine Hokkaido University Life Science Research Institute Kinki University Department of Pharmacology Kinki University Faculty of Medicine Department of Pathology Kinki University Faculty of Medicine Graduate School of Nutritional and Environmental Sciences University of Shizuoka

AIM: To investigate the(-)-epigallocatechin-3-gallate(EGCG) binding to transforming growth factor-β(TGF-β) type Ⅱ receptor(TGFRⅡ).METHODS: The expression of α-smooth muscle actin(α-SMA) was used as a marker for fibrotic change inhuman lung fibroblast MRC-5 cells. The α-SMA expression level was determined by western blotting and immunohistological analysis. We examined whether the anti-fibrotic effects of EGCG on MRC-5 cells was dependent on antioxidant mechanism by using edaravone and N-acetylcysteine(NAC). The suppression effects of EGCG on Smad2/3 activation were studied by confocal fluorescence microscopy. The binding of EGCG to recombinant TGFRⅡ protein was analyzed by immunoprecipitation and affinity ***: When MRC-5 cells were treated with TGF-β, EGCG decreased the expression of α-SMA in a dose dependent manner, whereas catechin did not influence the α-SMA expression in the cells. Except for EGCG, antioxidant compounds(e.g., edaravone and NAC) had no effects on the TGF-β-induced α-SMA expression. Nuclear localization of phosphorylated Smad2/3 was observed after TGF-β treatment; however, EGCG treatment attenuated the nuclear transportation of Smad2/3 in the presence or absence of TGF-β. After a TGFRⅡ expression vector was introduced into COS-7 cells, cell lysates were untreated or treated with EGCG or catechin. The immunoprecipitation experiments using the lysates showed that EGCG dose-dependently bound to TGFRⅡ and that catechin did not at all. Affinity chromatography study indicated that EGCG would bind to TGFRⅡ.CONCLUSION: Our results demonstrate that EGCG interacts with TGFRⅡ and inhibits the expression of α-SMA via the TGF-β-Smad2/3 pathway in human lung fibroblast MRC-5 cells.

关键词： Epigallocatechin-3-gallate Transforming growth factor-β Myofibroblast α-smooth muscle actin Fibrosis

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Risk factors for perforation during endoscopic retrograde cholangiopancreatography in post-reconstruction intestinal tract

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World Journal of Clinical Cases 2019年第1期7卷 10-18页

作者： Shinichi Takano Mitsuharu Fukasawa Hiroko Shindo Ei Takahashi sumio Hirose Yoshimitsu Fukasawa Satoshi Kawakami Hiroshi hayakawa Hiroshi Yokomichi Makoto Kadokura Tadashi Sato Nobuyuki Enomoto First Department of Internal Medicine Faculty of Medicine University of Yamanashi Yamanashi 409-3898 Japan Department of Health Sciences Interdisciplinary Graduate School and Engineering University of Yamanashi Yamanashi 409-3898 Japan

BACKGROUND Endoscopic retrograde cholangiopancreatography(ERCP) in patients with surgically altered anatomy has been a major challenge to gastrointestinal endoscopists with low success rates for reaching the target site as well as high complication rates. The knowledge of ERCP-related risk factors is important for reducing unexpected *** To identify ERCP-related risk factors for perforation in patients with surgically altered *** The medical records of 187 patients with surgically altered anatomy who underwent ERCP at our institution between April 2009 and December 2017 were retrospectively reviewed. An analysis of patient data, including age, sex, type of reconstruction, cause of surgery, aim of ERCP, success rate of reaching target site,success rate of procedure, adverse events, type of scope, time to reach the target site, and duration of procedure, was performed. In patients with Billroth-Ⅱ reconstruction, additional potential risk factors were the shape of the inserted scope and whether the anastomosis was antecolic or *** All patients(n = 187) had surgical anatomy, such as Billroth-Ⅰ(n = 22), Billroth-Ⅱ(n = 33), Roux-en-Y(n = 54), Child, or Whipple reconstruction(n = 75). ERCP was performed for biliary drainage in 43 cases(23%), stone removal in 29 cases(16%),and stricture dilation of anastomosis in 59 cases(32%). The scope was unable to reach the target site in 17 cases(9%), and an aimed procedure could not be accomplished in 54 cases(29%). Adverse events were pancreatitis(3%),hyperamylasemia(10%), cholangitis(6%), cholestasis(4%), excessive sedation(1%), perforation(2%), and others(3%). Perforation occurred in three cases, all of which were in patients with Billroth-Ⅱ reconstruction; in these patients, further analysis revealed loop-shaped insertion of the scope to be a significant risk for perforation(P = 0.01).CONCLUSION Risk factors for perforation during ERCP in patients with surgically altered anatomy were Billro

关键词： Surgically altered anatomy Billroth-Ⅱ Endoscopic retrograde cholangiopancreatography Perforation

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