1 Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine , Seoul, Korea.
Antioxid Redox Signal. 2014 Jun 10;20(17):2854-72. doi: 10.1089/ars.2013.5619. Epub 2014 Jan 24.
Hepatic fibrosis is the common pathophysiologic process resulting from chronic liver injury, characterized by the accumulation of an excessive extracellular matrix. Multiple lines of evidence indicate that oxidative stress plays a pivotal role in the pathogenesis of liver fibrosis. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX) is a multicomponent enzyme complex that generates reactive oxygen species (ROS) in response to a wide range of stimuli. In addition to phagocytic NOX2, there are six nonphagocytic NOX proteins.
In the liver, NOX is functionally expressed both in the phagocytic form and in the nonphagocytic form. NOX-derived ROS contributes to various kinds of liver disease caused by alcohol, hepatitis C virus, and toxic bile acids. Recent evidence indicates that both phagocytic NOX2 and nonphagocytic NOX isoforms, including NOX1 and NOX4, mediate distinct profibrogenic actions in hepatic stellate cells, the main fibrogenic cell type in the liver. The critical role of NOX in hepatic fibrogenesis provides a rationale to assess pharmacological NOX inhibitors that treat hepatic fibrosis in patients with chronic liver disease.
Although there is compelling evidence indicating a crucial role for NOX-mediated ROS generation in hepatic fibrogenesis, little is known about the expression, subcellular localization, regulation, and redox signaling of NOX isoforms in specific cell types in the liver. Moreover, the exact mechanism of NOX-mediated fibrogenic signaling is still largely unknown.
A better understanding through further research about NOX-mediated fibrogenic signaling may enable the development of novel anti-fibrotic therapy using NOX inhibition strategy. Antio
肝纤维化是慢性肝损伤导致的常见病理生理过程，其特征是细胞外基质的过度积累。大量证据表明氧化应激在肝纤维化的发病机制中起关键作用。烟酰胺腺嘌呤二核苷酸磷酸（NADPH）氧化酶（NOX）是一种多成分酶复合物，可响应广泛的刺激产生活性氧（ROS）。除吞噬性 NOX2 外，还有 6 种非吞噬性 NOX 蛋白。
在肝脏中，NOX 以吞噬形式和非吞噬形式功能性表达。NOX 衍生的 ROS 有助于由酒精、丙型肝炎病毒和毒性胆汁酸引起的各种肝病。最近的证据表明，吞噬性 NOX2 和非吞噬性 NOX 同工型，包括 NOX1 和 NOX4，在肝星状细胞中介导不同的促纤维化作用，肝星状细胞是肝脏中主要的纤维生成细胞类型。NOX 在肝纤维化中的关键作用为评估治疗慢性肝病患者肝纤维化的药理学 NOX 抑制剂提供了依据。
尽管有令人信服的证据表明 NOX 介导的 ROS 生成在肝纤维化中起关键作用，但对于 NOX 同工型在肝脏特定细胞类型中的表达、亚细胞定位、调节和氧化还原信号仍知之甚少。此外，NOX 介导的纤维生成信号的具体机制仍在很大程度上未知。
通过进一步研究更好地了解 NOX 介导的纤维生成信号可能会启用使用 NOX 抑制策略的新型抗纤维化治疗。
