NADPH oxidase enzymes in skin fibrosis: molecular targets and therapeutic agents.
NADPH oxidase enzymes in skin fibrosis: molecular targets and therapeutic agents.
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DOI：
10.1007/s00403-013-1416-8
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发表时间：
2014-05
影响因子：
3
通讯作者：
Jagdeo J
中科院分区：
文献类型：
--
作者：
Babalola O;Mamalis A;Lev-Tov H;Jagdeo J
纤维化的特点是细胞外基质成分过度沉积，最终导致器官功能障碍和衰竭。在皮肤病学中，纤维化是许多皮肤病的标志性组成部分，包括系统性硬化症、移植物抗宿主病、肥厚性疤痕、瘢痕疙瘩、肾源性系统性纤维化、迟发性皮肤卟啉症、限制性皮肤病和其他疾病。纤维化性皮肤疾病可能使人衰弱并影响生活质量。fda批准的抗纤维化药物很少；因此，这一领域的研究对于解决这一缺陷至关重要。最近的研究表明，皮肤纤维化的发病机制与多组分烟酰胺腺嘌呤二核苷酸磷酸（NADPH）氧化酶（Nox）酶复合物产生的内源性活性氧有关。本文就氮氧化物酶及其在皮肤纤维化中的作用作一综述。概述了氮氧化物酶家族和他们的作用在皮肤纤维化的发病机制进行了讨论。对Nox酶影响特定皮肤纤维化疾病的机制也进行了综述。最后，我们描述了通过使用他汀类药物、p47phox亚基调节剂或GKT137831（一种Nox酶的竞争性抑制剂）直接靶向Nox酶来改善皮肤纤维化的治疗方法。氮氧化物酶也可以通过抗氧化剂清除活性氧间接靶向。我们认为，Nox调节剂值得进一步研究，并有可能改变皮肤科医生对皮肤纤维化的管理。
Fibrosis is characterized by the excessive deposition of extracellular matrix components eventually resulting in organ dysfunction and failure. In dermatology, fibrosis is the hallmark component of many skin diseases, including systemic sclerosis, graft versus host disease, hypertrophic scars, keloids, nephrogenic systemic fibrosis, porphyria cutanea tarda, restrictive dermopathy and other conditions. Fibrotic skin disorders may be debilitating and impair quality of life. There are few FDA-approved anti-fibrotic drugs; thus, research in this area is crucial in addressing this deficiency. Recent investigations elucidating the pathogenesis of skin fibrosis have implicated endogenous reactive oxygen species produced by the multicomponent nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (Nox) enzyme complex. In this review we discuss Nox enzymes and their role in skin fibrosis. An overview of the Nox enzyme family is presented and their role in the pathogenesis of skin fibrosis is discussed. The mechanisms that Nox enzymes influence specific skin fibrotic disorders are also reviewed. Finally, we describe the therapeutic approaches to ameliorate skin fibrosis by directly targeting Nox enzymes with the use of statins, p47phox subunit modulators, or GKT137831, a competitive inhibitor of Nox enzymes. Nox enzymes can also be targeted indirectly via scavenging ROS with antioxidants. We believe that Nox modulators are worthy of further investigation and have the potential to transform the management of skin fibrosis by dermatologists.
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影响因子：
8
作者：
Altenhofer, Sebastian;Kleikers, Pamela W. M.;Radermacher, Kim A.;Scheurer, Peter;Hermans, J. J. Rob;Schiffers, Paul;Ho, Heidi;Wingler, Kirstin;Schmidt, Harald H. H. W.
通讯作者：
Schmidt, Harald H. H. W.
影响因子：
3.9
作者：
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通讯作者：
Bloxham, David P.
影响因子：
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作者：
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通讯作者：
Nacca M
影响因子：
13.5
作者：
Aoyama, Tomonori;Paik, Yong-Han;Watanabe, Sumio;Laleu, Benoit;Gaggini, Francesca;Fioraso-Cartier, Laetitia;Molango, Sophie;Heitz, Freddy;Merlot, Cedric;Szyndralewiez, Cedric;Page, Patrick;Brenner, David A.
通讯作者：
Brenner, David A.
影响因子：
15.9
作者：
Bataller, R;Schwabe, RF;Brenner, DA
通讯作者：
Brenner, DA