Inhibition of transglutaminase 2 enzymatic activity ameliorates the anti-angiogenic effects of coeliac disease autoantibodies

被引：13

作者：

Caja, Sergio ^{[1
]}

Myrsky, Essi ^{[1
]}

Korponay-Szabo, Ilma R. ^{[2
,3
]}

Nadalutti, Cristina ^{[1
]}

Sulic, Ana-Marija ^{[4
]}

Lavric, Miha ^{[4
]}

Sblatter, Daniele ^{[5
]}

Marzari, Roberto ^{[4
]}

Collighan, Russell ^{[6
]}

Mongeot, Alexandre ^{[7
]}

Griffin, Martin ^{[6
]}

Maki, Markku ^{[1
,8
]}

Kaukinen, Katri ^{[1
,9
]}

Lindfors, Katri ^{[1
]}

机构：

[1] Univ Tampere, Sch Med, Paediat Res Ctr, FIN-33014 Tampere, Finland

[2] Heim Pal Childrens Hosp, Budapest, Hungary

[3] Univ Debrecen, Med & Hlth Sci Ctr, Dept Paediat, H-4012 Debrecen, Hungary

[4] Univ Trieste, Dept Biol, Trieste, Italy

[5] Univ Piemonte Orientale, Dept Med Sci, Novara, Italy

[6] Aston Univ, Sch Life & Hlth Sci, Birmingham B4 7ET, W Midlands, England

[7] X Link, Nottingham, England

[8] Tampere Univ Hosp, Dept Paediat, Tampere, Finland

[9] Tampere Univ Hosp, Dept Gastroenterol & Alimentary Tract Surg, Tampere, Finland

来源：

SCANDINAVIAN JOURNAL OF GASTROENTEROLOGY | 2010年 / 45卷 / 04期

基金：

匈牙利科学研究基金会; 芬兰科学院;

关键词：

Autoantibodies; coeliac disease; transglutaminase; 2; activity; TISSUE TRANSGLUTAMINASE; RETINOIC ACID; IN-VIVO; DIFFERENTIATION; ACTIVATION; VITRO;

D O I：

10.3109/00365520903540822

中图分类号：

R57 [消化系及腹部疾病];

学科分类号：

摘要：

Objective. Earlier work has demonstrated that serum autoantibodies from coeliac patients targeted against transglutaminase 2 (TG2) inhibit in vitro angiogenesis. The aim of this study was to establish whether coeliac patient-derived monoclonal TG2-targeted antibodies produced by recombination technology exert similar anti-angiogenic effects to serum-derived coeliac autoantibodies. In addition, we studied whether the monoclonal patient autoantibodies modulate endothelial cell TG2 activity and whether such modulation is related to the anti-angiogenic effects. Material and methods. The influence of coeliac patient-derived monoclonal TG2-targeted antibodies on endothelial cell tubule formation was studied using a three-dimensional angiogenic cell culture model. Endothelial cell TG2 enzymatic activity was determined by means of a live-cell enzyme-linked immunosorbent assay. Results. Coeliac patient-derived monoclonal TG2-targeted antibodies produced by recombination technology inhibited endothelial tubule formation and enhanced the crosslinking activity of TG2. When this enzymatic activity was inhibited using site-directed irreversible TG2 inhibitors in the presence of autoantibodies, in vitro angiogenesis reverted to the control level. Conclusions. Since we found a significant negative correlation between endothelial cell angiogenesis and TG2 activity, we suggest that the anti-angiogenic effects of coeliac patient-derived TG2-targeted autoantibodies are exerted by enhanced enzymatic activity of TG2.

引用

页码：421 / 427

页数：7

共 27 条

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