Reactive nitrogen species augment fibroblast-mediated collagen gel contraction, mediator production, and chemotaxis.

Reactive nitrogen species augment fibroblast-mediated collagen gel contraction, mediator production, and chemotaxis.
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活性氮增强成纤维细胞介导的胶原凝胶收缩、介质产生和趋化性。

DOI:
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发表时间:
2006
影响因子:
6.4
通讯作者:
S. Rennard
S. Rennard
中科院分区:
医学1区
文献类型:
--
作者:
H. Sugiura;Xiangde Liu;Tetsu Kobayashi;S. Togo;R. Ertl;S. Kawasaki;K. Kamio;Xingqi Wang;L. Mao;Lei Shen;C. Hogaboam;S. Rennard

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过氧亚硝酸盐等活性氮 (RNS) 会导致细胞损伤和组织炎症。在哮喘和慢性阻塞性肺病(以组织重塑为特征的疾病)患者的气道中观察到硝基酪氨酸的过量产生,硝基酪氨酸是 RNS 的足迹。本研究的目的是评估 RNS 是否可以通过对成纤维细胞的直接影响来影响组织重塑,并确定这些影响是否取决于转化生长因子-β (TGF-β) 的产生。为了实现这一目标,使用人胎儿肺成纤维细胞(HFL-1)来评估成纤维细胞介导的浮动凝胶收缩和对纤连蛋白的趋化性。此外,通过酶联免疫吸附测定评估成纤维细胞释放 TGF-β1、纤连蛋白和血管内皮生长因子 (VEGF) 的能力。与对照相比,纯过氧亚硝酸盐以浓度依赖性方式显着增强凝胶收缩(P < 0.01)和趋化性(P < 0.01)。同样,过氧亚硝酸盐供体 3-吗啉代苷亚胺盐酸盐 (SIN-1) 也增强了凝胶收缩 (P < 0.01)。在 3D 凝胶和单层培养中,RNS 还显着增加了 TGF-β1 (P < 0.01)、纤连蛋白 (P < 0.01) 和 VEGF (P < 0.01) 释放到培养基中。抗 TGF-β 抗体可逆转 RNS 增强的凝胶收缩 (P < 0.01) 和介质产生 (P < 0.01)。抗 TGF-β 抗体也部分但显着地逆转了 RNS 增强的纤连蛋白趋化性(P < 0.01)。最后,过氧亚硝酸盐增强了α5β1整合素的表达,α5β1整合素是纤连蛋白的受体(P<0.01),并且中和抗TGF-β抗体抑制了过氧亚硝酸盐增强的α5β1表达(P<0.01)。这些结果表明RNS可以通过调节TGF-β1影响组织修复过程。
Reactive nitrogen species (RNS) such as peroxynitrite cause cellular injury and tissue inflammation. Excessive production of nitrotyrosine, which is a footprint of RNS, has been observed in the airways of patients with asthma and chronic obstructive pulmonary disease, disorders characterized by tissue remodeling. The aim of this study was to evaluate whether RNS can affect tissue remodeling through direct effects on fibroblasts, and to determine if these effects depend on production of transforming growth factor-beta (TGF-beta). To accomplish this, human fetal lung fibroblasts (HFL-1) were used to assess fibroblast-mediated contraction of floating gels and chemotaxis toward fibronectin. In addition, the ability of fibroblasts to release TGF-beta1, fibronectin, and vascular endothelial growth factor (VEGF) was assessed by enzyme-linked immunosorbent assay. Authentic peroxynitrite significantly augmented gel contraction (P < 0.01) and chemotaxis (P < 0.01) compared with control in a concentration-dependent manner. Similarly, the peroxynitrite donor 3-morpholynosidenonimine hydrochloride (SIN-1) also augmented gel contraction (P < 0.01). RNS also significantly increased TGF-beta1 (P < 0.01), fibronectin (P < 0.01), and VEGF (P < 0.01) release into the media in both 3D gel and monolayer culture. Anti-TGF-beta antibody reversed RNS-augmented gel contraction (P < 0.01) and mediator production (P < 0.01). Anti-TGF-beta antibody also partially, but significantly, reversed RNS-augmented chemotaxis toward fibronectin (P < 0.01). Finally, peroxynitrite enhanced expression of alpha5beta1 integrin, which is a receptor for fibronectin (P < 0.01), and neutralizing anti-TGF-beta antibody suppressed peroxynitrite-augmented alpha5beta1 expression (P < 0.01). These results suggest that RNS can affect the tissue repair process by modulating TGF-beta1.
一氧化氮、超氧化物和过氧亚硝酸盐:好的、坏的和丑陋的。
DOI: 10.1152/ajpcell.1996.271.5.c1424
发表时间: 1996
期刊: The American journal of physiology
影响因子: --
作者:
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发表时间: 1990-02-01
影响因子: 11.1
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发表时间: 1999
期刊: American journal of respiratory and critical care medicine.
影响因子: --
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DOI: 10.1378/chest.122.6_suppl.314s
发表时间: 2002-12-01
期刊: CHEST
影响因子: 9.6
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