IUF-Leibniz-Research Institute for Environmental Medicine, 40225 Düsseldorf, Germany.
Laboratory of Experimental Dermatology, Department of Dermatology, Otto-von-Guericke University, 39120 Magdeburg, Germany.
Int J Mol Sci. 2019 Nov 28;20(23):6005. doi: 10.3390/ijms20236005.
The skin is constantly exposed to a variety of environmental threats, including solar electromagnetic radiation, microbes, airborne particulate matter, and chemicals. Acute exposure to these environmental factors results in the activation of different signaling pathways that orchestrate adaptive stress responses to maintain cell and tissue homeostasis. Chronic exposure of skin to these factors, however, may lead to the accumulation of damaged macromolecules and loss of cell and tissue integrity, which, over time, may facilitate aging processes and the development of aging-related malignancies. One transcription factor that is expressed in all cutaneous cells and activated by various environmental stressors, including dioxins, polycyclic aromatic hydrocarbons, and ultraviolet radiation, is the aryl hydrocarbon receptor (AHR). By regulating keratinocyte proliferation and differentiation, epidermal barrier function, melanogenesis, and immunity, a certain degree of AHR activity is critical to maintain skin integrity and to adapt to acute stress situations. In contrast, a chronic activation of cutaneous AHR signaling critically contributes to premature aging and the development of neoplasms by affecting metabolism, extracellular matrix remodeling, inflammation, pigmentation, DNA repair, and apoptosis. This article provides an overview of the detrimental effects associated with sustained AHR activity in chronically stressed skin and pinpoints AHR as a promising target for chemoprevention.
皮肤不断暴露于各种环境威胁中，包括太阳电磁辐射、微生物、空气传播的颗粒物和化学物质。急性暴露于这些环境因素会激活不同的信号通路，协调适应性应激反应，以维持细胞和组织的内稳态。然而，皮肤慢性暴露于这些因素可能导致受损大分子的积累和细胞及组织完整性的丧失，随着时间的推移，这可能促进衰老过程和与衰老相关的恶性肿瘤的发展。一种在所有皮肤细胞中表达并被各种环境应激源（如二恶英、多环芳烃和紫外线）激活的转录因子是芳香烃受体（AHR）。通过调节角质形成细胞的增殖和分化、表皮屏障功能、黑色素生成和免疫，一定程度的 AHR 活性对于维持皮肤完整性和适应急性应激情况至关重要。相比之下，皮肤 AHR 信号的慢性激活通过影响代谢、细胞外基质重塑、炎症、色素沉着、DNA 修复和细胞凋亡，严重促进皮肤过早衰老和肿瘤的发生。本文概述了慢性应激皮肤中持续 AHR 活性相关的有害影响，并指出 AHR 是化学预防的一个有前途的靶点。
