N-乙酰半胱氨酸抑制 TGF-β1 诱导的成纤维细胞的纤维生成反应。
N-acetyl-L-cysteine inhibits TGF-beta1-induced profibrotic responses in fibroblasts.
机构信息
Third Department of Internal Medicine, Wakayama Medical University School of Medicine, 811-1 Kimiidera, Wakayama, Wakayama 641-0012, Japan.
出版信息
Pulm Pharmacol Ther. 2009 Dec;22(6):487-91. doi: 10.1016/j.pupt.2009.04.002. Epub 2009 Apr 22.
BACKGROUND
Excessive production of TGF-beta(1) plays a key role in the tissue remodeling or fibrotic process observed in bronchial asthma, chronic pulmonary disease (COPD), and idiopathic pulmonary fibrosis (IPF). TGF-beta(1) has been reported to decrease the intracellular glutathione level and stimulate the production of reactive oxygen species.
OBJECTIVES
The aim of this study was to evaluate whether the antioxidant N-acetyl-l-cysteine (NAC) can affect TGF-beta(1)-mediated tissue remodeling in fibroblasts or modulate the production of fibronectin and vascular endothelial growth factor (VEGF) which are believed to be important mediators of tissue repair and remodeling.
METHODS
To accomplish this, human fetal lung fibroblasts (HFL-1) were used to assess the effect of NAC on the TGF-beta(1)-mediated contraction of floating gels and the TGF-beta(1)-induced mediator production. In addition, the effect of NAC on the TGF-beta(1)-induced differentiation to myofibroblasts was evaluated by assessing alpha-smooth muscle actin (alpha-SMA) expression.
RESULTS
NAC significantly abolished the TGF-beta(1)-augmented gel contraction (at 3mM, gel size 63.4+/-2.6% vs. 39.1+/-4.1%; p<0.01) compared with control in a concentration-dependent manner. NAC also significantly inhibited the TGF-beta(1)-augmented fibronectin (p<0.01) and VEGF (p<0.01) production in the media of both the three-dimensional gel and monolayer culture. Furthermore, NAC reversed the TGF-beta(1)-stimulated alpha-SMA expression (p<0.01).
CONCLUSION
These results suggest that NAC can affect the TGF-beta(1)-induced tissue remodeling or fibrotic process in vitro.
背景
转化生长因子-β1（TGF-β1）的过度产生在支气管哮喘、慢性肺部疾病（COPD）和特发性肺纤维化（IPF）中观察到的组织重塑或纤维化过程中起着关键作用。据报道，TGF-β1 会降低细胞内谷胱甘肽水平并刺激活性氧的产生。
目的
本研究旨在评估抗氧化剂 N-乙酰-L-半胱氨酸（NAC）是否可以影响成纤维细胞中 TGF-β1 介导的组织重塑，或调节纤连蛋白和血管内皮生长因子（VEGF）的产生，这被认为是组织修复和重塑的重要介质。
方法
为此，使用人胎肺成纤维细胞（HFL-1）评估 NAC 对 TGF-β1 介导的漂浮凝胶收缩和 TGF-β1 诱导的介质产生的影响。此外，通过评估α-平滑肌肌动蛋白（α-SMA）表达来评估 NAC 对 TGF-β1 诱导的向肌成纤维细胞分化的影响。
结果
NAC 以浓度依赖的方式显著消除了 TGF-β1 增强的凝胶收缩（在 3mM 时，凝胶大小为 63.4+/-2.6%比 39.1+/-4.1%；p<0.01）。NAC 还显著抑制了三维凝胶和单层培养物培养基中 TGF-β1 增强的纤连蛋白（p<0.01）和 VEGF（p<0.01）的产生。此外，NAC 逆转了 TGF-β1 刺激的α-SMA 表达（p<0.01）。
结论
这些结果表明，NAC 可以影响 TGF-β1 诱导的组织重塑或纤维化过程在体外。
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