Department of Dermatology, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China; Hunan Key Laboratory of Medical Epigenetics, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China.
Department of Anesthesiology, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China; Clinical Nursing Teaching and Research Section, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China.
Int Immunopharmacol. 2023 Mar;116:109764. doi: 10.1016/j.intimp.2023.109764. Epub 2023 Jan 25.
Scleroderma is an autoimmune disease mainly characterized by progressive fibrosis of the skin. There are two types of scleroderma, namely localized scleroderma (LS) and systemic sclerosis (SSc); skin lesions in both types of scleroderma are histologically identical. Progressive skin sclerosis induces psychological and ecological burden for scleroderma patients. However, there is no effective treatment for scleroderma due to its unclear etiology. Aryl hydrocarbon receptor (AhR) is recognized as an environmental chemical effector that can respond to ultraviolet radiation, which has been demonstrated to participate in the pathogenesis of SSc in our previous study. In this study, we verify whether the anti-fibrosis effect of ultraviolet A1 (UVA1) phototherapy could be partially induced through Ficz/AhR/MAPK signaling activation for fibrotic lesions in both SSc and LS patients. This is the first study to show the association between the AhR pathway and the anti-fibrotic mechanism of UVA1 phototherapy, which provides additional evidence of the role of AhR in the fibrotic mechanism of systemic scleroderma from different perspectives. Ficz and other AhR agonists may replace UVA1 phototherapy as anti-fibrotic agents in scleroderma.
硬皮病是一种自身免疫性疾病，主要表现为皮肤进行性纤维化。硬皮病有两种类型，即局限性硬皮病（LS）和系统性硬皮病（SSc）；两种类型的硬皮病的皮肤病变在组织学上是相同的。进行性皮肤硬化会给硬皮病患者带来心理和生态负担。然而，由于其病因不明，目前尚无有效的治疗方法。芳基烃受体（AhR）被认为是一种环境化学效应物，可对紫外线辐射作出反应，我们之前的研究已经证明其参与了 SSc 的发病机制。在这项研究中，我们验证了 UVA1 光疗的抗纤维化作用是否可以通过 Ficz/AhR/MAPK 信号通路激活来部分诱导，从而治疗 SSc 和 LS 患者的纤维化病变。这是第一项研究表明 AhR 途径与 UVA1 光疗的抗纤维化机制之间存在关联的研究，从不同角度为 AhR 在系统性硬皮病的纤维化机制中的作用提供了额外的证据。Ficz 和其他 AhR 激动剂可能会取代 UVA1 光疗作为硬皮病的抗纤维化药物。
