Department of Medicine, Division of Pulmonary, Allergy and Critical Care and Sleep Medicine, University of Arizona, Tucson, AZ, 85724, United States.
Department of Medicine, Division of Pulmonary, Allergy and Critical Care and Sleep Medicine, University of Arizona, Tucson, AZ, 85724, United States; Southern Arizona VA Health Care System (SAVAHCS), Tucson, AZ, 85723, United States.
Redox Biol. 2020 Jun;33:101541. doi: 10.1016/j.redox.2020.101541. Epub 2020 Apr 17.
Oxidative stress has been associated with a number of human fibrotic diseases, including idiopathic pulmonary fibrosis (IPF). Although oxidative stress is associated with both fibrosis and aging, the precise cellular sources(s) of reactive oxygen species (ROS) that contribute to the disease pathogenesis remain poorly understood. NADPH oxidase (Nox) enzymes are an evolutionarily conserved family, where their only known function is the production of ROS. A growing body of evidence supports a link between excessive Nox-derived ROS and numerous chronic diseases (including fibrotic disease), which is most prevalent among the elderly population. In this review, we examine the evidence for Nox isoforms in the pathogenesis of IPF, and the potential to target this enzyme family for the treatment of IPF and related fibrotic disorders. A better understanding of the Nox-mediated redox imbalance in aging may be critical to the development of more effective therapeutic strategies for age-associated fibrotic disorders. Strategies aimed at specifically blocking the source(s) of ROS through Nox inhibition may prove to be more effective as anti-fibrotic therapies, as compared to antioxidant approaches. This review also discusses the potential of Nox-targeting therapeutics currently in development.
氧化应激与许多人类纤维化疾病有关，包括特发性肺纤维化 (IPF)。尽管氧化应激与纤维化和衰老都有关，但导致疾病发病机制的确切细胞来源（s）的活性氧 (ROS) 仍知之甚少。NADPH 氧化酶 (Nox) 酶是一个进化上保守的家族，其唯一已知的功能是产生 ROS。越来越多的证据表明，过多的 Nox 衍生的 ROS 与许多慢性疾病（包括纤维化疾病）之间存在联系，而这些疾病在老年人群中最为普遍。在这篇综述中，我们研究了 Nox 同工型在 IPF 发病机制中的作用，以及针对该酶家族治疗 IPF 和相关纤维化疾病的潜力。更好地了解 Nox 介导的氧化还原失衡在衰老中的作用，对于开发针对与年龄相关的纤维化疾病的更有效的治疗策略可能至关重要。与抗氧化方法相比，通过 Nox 抑制特异性阻断 ROS 来源的策略可能更有效地作为抗纤维化疗法。这篇综述还讨论了目前正在开发的针对 Nox 的治疗药物的潜力。
