Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA.
Antioxid Redox Signal. 2020 Aug 20;33(6):455-479. doi: 10.1089/ars.2020.8032. Epub 2020 Mar 4.
Fibrosis is a stereotypic, multicellular tissue response to diverse types of injuries that fundamentally result from a failure of cell/tissue regeneration. This complex tissue remodeling response disrupts cellular/matrix composition and homeostatic cell-cell interactions, leading to loss of normal tissue architecture and progressive loss of organ structure/function. Fibrosis is a common feature of chronic diseases that may affect the lung, kidney, liver, and heart. There is emerging evidence to support a combination of genetic, environmental, and age-related risk factors contributing to susceptibility and/or progression of fibrosis in different organ systems. A core pathway in fibrogenesis involving these organs is the induction and activation of nicotinamide adenine dinucleotide phosphate oxidase (NOX) family enzymes. We explore current pharmaceutical approaches to targeting NOX enzymes, including repurposing of currently U.S. Food and Drug Administration (FDA)-approved drugs. Specific inhibitors of various NOX homologs will aid establishing roles of NOXs in the various organ fibroses and potential efficacy to impede/halt disease progression. The discovery of novel and highly specific NOX inhibitors will provide opportunities to develop NOX inhibitors for treatment of fibrotic pathologies.
纤维化是一种对多种类型损伤的典型、多细胞组织反应，其根本原因是细胞/组织再生失败。这种复杂的组织重塑反应破坏了细胞/基质组成和细胞间的稳态相互作用，导致正常组织结构的丧失和器官结构/功能的进行性丧失。纤维化是可能影响肺、肾、肝和心脏的慢性疾病的共同特征。有越来越多的证据支持遗传、环境和与年龄相关的风险因素共同导致不同器官系统纤维化的易感性和/或进展。涉及这些器官的纤维化形成的核心途径是烟酰胺腺嘌呤二核苷酸磷酸氧化酶（NOX）家族酶的诱导和激活。我们探讨了针对 NOX 酶的当前药物方法，包括重新利用目前美国食品和药物管理局（FDA）批准的药物。各种 NOX 同源物的特定抑制剂将有助于确定 NOX 在各种器官纤维化中的作用以及潜在的疗效，以阻止/阻止疾病进展。新型和高度特异性 NOX 抑制剂的发现将为开发用于治疗纤维化病理的 NOX 抑制剂提供机会。
