Role of N-acetylcysteine and GSH redox system on total and active MMP-2 in intestinal myofibroblasts of Crohn's disease patients.
Role of N-acetylcysteine and GSH redox system on total and active MMP-2 in intestinal myofibroblasts of Crohn's disease patients.
复制标题
DOI：
10.1007/s00384-012-1632-2
复制
发表时间：
2013-07
影响因子：
2.8
通讯作者：
Iantomasi T
中科院分区：
文献类型：
--
作者：
Romagnoli C;Marcucci T;Picariello L;Tonelli F;Vincenzini MT;Iantomasi T
Intestinal subepithelial myofibroblasts (ISEMFs)1 are the predominant source of matrix metalloproteinase-2 (MMP-2) in gut, and a decrease in glutathione/oxidized glutathione (GSH/GSSG) ratio, intracellular redox state index, occurs in the ISEMFs of patients with Crohn’s disease (CD). The aim of this study is to demonstrate a relationship between MMP-2 secretion and activation and changes of GSH/GSSG ratio in ISEMFs stimulated or not with tumor necrosis factor alpha (TNFα). ISEMFs were isolated from ill and healthy colon mucosa of patients with active CD. Buthionine sulfoximine, GSH synthesis inhibitor, and N-acetylcysteine (NAC), precursor of GSH synthesis, were used to modulate GSH/GSSG ratio. GSH and GSSG were measured by HPLC and MMP-2 by ELISA Kit. In cells, stimulated or not with TNFα, a significant increase in MMP-2 secretion and activation, related to increased oxidative stress, due to low GSH/GSSG ratio, was detected. NAC treatment, increasing this ratio, reduced MMP-2 secretion and exhibited a direct effect on the secreted MMP-2 activity. In NAC-treated and TNFα-stimulated ISEMFs of CD patients’ MMP-2 activity were restored to physiological value. The involvement of c-Jun N-terminal kinase pathway on redox regulation of MMP-2 secretion has been demonstrated. For the first time, in CD patient ISEMFs, a redox regulation of MMP-2 secretion and activation related to GSH/GSSG ratio and inflammatory state have been demonstrated. This study suggests that compounds able to maintain GSH/GSSG ratio to physiological values can be useful to restore normal MMP-2 levels reducing in CD patient intestine the dysfunction of epithelial barrier.
登录
查看更多内容
影响因子：
29.4
作者：
Di Sabatino, Antonio;Pender, Sylvia L. F.;Macdonald, Thomas T.
通讯作者：
Macdonald, Thomas T.
影响因子：
1.9
作者：
Okuno, T;Andoh, A;Bamba, T
通讯作者：
Bamba, T
影响因子：
6
作者：
McKaig, BC;McWilliams, D;Mahida, YR
通讯作者：
Mahida, YR
DOI：
10.1152/ajpgi.00494.2001
发表时间：
2002-06-01
影响因子：
4.5
作者：
Hata, K;Andoh, A;Bamba, T
通讯作者：
Bamba, T
影响因子：
4.6
作者：
Mahida, YR;Galvin, AM;Podolsky, DK
通讯作者：
Podolsky, DK