Reciprocal regulation of TGF-β and reactive oxygen species: A perverse cycle for fibrosis.
Reciprocal regulation of TGF-β and reactive oxygen species: A perverse cycle for fibrosis.
复制标题
TGF-β和活性氧的相互调节：纤维化的不良周期。
DOI：
10.1016/j.redox.2015.09.009
复制
发表时间：
2015-12
期刊：
影响因子：
11.4
通讯作者：
Desai LP
中科院分区：
文献类型：
--
作者：
Liu RM;Desai LP
转化生长因子β (TGF-β) 是最有效的促纤维化细胞因子，其表达在几乎所有纤维化疾病中都会增加。尽管通过 Smad 途径的信号传导被认为在 TGF-β 的纤维形成中发挥核心作用，但新出现的证据表明，活性氧 (ROS) 通过包括 Smad 途径在内的不同途径调节 TGF-β 的信号传导。 TGF-β1 增加 ROS 的产生并抑制抗氧化酶，导致氧化还原失衡。 ROS 反过来诱导/激活 TGF-β1 并介导许多 TGF-β 的纤维化作用，形成恶性循环（参见右图流程图）。在这里，我们回顾了目前关于纤维化发展中 TGF-β1 和 ROS 之间的前馈机制的知识。针对 TGF-β 诱导和 ROS 依赖性细胞信号传导的治疗代表了治疗纤维化疾病的新方法。 TGF-β1 是最有效、普遍存在的促纤维化细胞因子。 TGF-β1通过↑ROS产生和↓抗氧化防御系统氧化还原失衡诱导氧化还原失衡，反过来，激活潜在的TGF-β1并诱导TGF-β1表达。氧化还原失衡还介导 TGF-β1 的许多促纤维化作用
Transforming growth factor beta (TGF-β) is the most potent pro-fibrogenic cytokine and its expression is increased in almost all of fibrotic diseases. Although signaling through Smad pathway is believed to play a central role in TGF-β's fibrogenesis, emerging evidence indicates that reactive oxygen species (ROS) modulate TGF-β's signaling through different pathways including Smad pathway. TGF-β1 increases ROS production and suppresses antioxidant enzymes, leading to a redox imbalance. ROS, in turn, induce/activate TGF-β1 and mediate many of TGF-β's fibrogenic effects, forming a vicious cycle (see graphic flow chart on the right). Here, we review the current knowledge on the feed-forward mechanisms between TGF-β1 and ROS in the development of fibrosis. Therapeutics targeting TGF-β-induced and ROS-dependent cellular signaling represents a novel approach in the treatment of fibrotic disorders. TGF-β1 is the most potent ubiquitous profibrogenic cytokine. TGF- β 1 induces redox imbalance by ↑ ROS production and ↓ anti-oxidant defense system Redox imbalance, in turn, activates latent TGF-β1 and induces TGF-β1 expression. Redox imbalance also mediates many of TGF-β1’s profibrogenic effects