Unfractionated Heparin and New Heparin Analogues from Ascidians (Chordate-Tunicate) Ameliorate Colitis in Rats

被引：45

作者：

Belmiro, Celso L. R. ^{[1
,2
]}

Castelo-Branco, Morgana T. L. ^{[3
]}

Melim, Leandra M. C. ^{[1
,2
]}

Schanaider, Alberto ^{[4
]}

Elia, Celeste ^{[5
]}

Madi, Kalil ^{[5
]}

Pavao, Mauro S. G. ^{[1
,2
]}

de Souza, Heitor S. P. ^{[5
]}

机构：

[1] Univ Fed Rio de Janeiro, Hosp Univ Clementino Fraga Filho, Lab Tecido Conjunt, BR-21941913 Rio De Janeiro, Brazil

[2] Univ Fed Rio de Janeiro, Inst Bioquim Med, BR-21941913 Rio De Janeiro, Brazil

[3] Univ Fed Rio de Janeiro, Inst Ciencias Biomed, Dept Histol & Embryol, BR-21941590 Rio de Janeiro, Brazil

[4] Univ Fed Rio de Janeiro, HUCFF, Dept Cirurgia Expt, BR-21941590 Rio de Janeiro, Brazil

[5] Univ Fed Rio de Janeiro, HUCFF, Dept Clin Med, BR-21941913 Rio de Janeiro, Brazil

来源：

JOURNAL OF BIOLOGICAL CHEMISTRY | 2009年 / 284卷 / 17期

关键词：

INFLAMMATORY-BOWEL-DISEASE; TUMOR-NECROSIS-FACTOR; FACTOR-KAPPA-B; CROHNS-DISEASE; FACTOR-ALPHA; ULCERATIVE-COLITIS; MOLECULAR-WEIGHT; ANTICOAGULANT ACTIVITY; INCREASED EXPRESSION; MAINTENANCE THERAPY;

D O I：

10.1074/jbc.M807211200

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

The anti-inflammatory effect of mammalian heparin analogues, named dermatan sulfate and heparin, isolated from the ascidian Styela plicata was accessed in a TNBS-induced colitis model in rats. Subcutaneous administration of the invertebrate compounds during a 7-day period drastically reduced inflammation as observed by the normalization of the macroscopic and histological characteristics of the colon. At the molecular level, a decrease in the production of TNF-alpha, TGF-beta, and VEGF was observed, as well as a reduction of NF-kappa B and MAPK kinase activation. At the cellular level, the heparin analogues attenuated lymphocyte and macrophage recruitment and epithelial cell apoptosis. Adrastic reduction in collagen-mediated fibrosis was also observed. No hemorrhagic events were observed after glycan treatment. These results strongly indicate the potential therapeutic use of these compounds for the treatment of colonic inflammation with a lower risk of hemorrhage when compared with mammalian heparin.

引用

页码：11267 / 11278

页数：12

共 62 条

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