Opsin 3 is a key regulator of ultraviolet A-induced photoageing in human dermal fibroblast cells
Opsin 3 is a key regulator of ultraviolet A-induced photoageing in human dermal fibroblast cells
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视蛋白 3 是紫外线 A 诱导的人真皮成纤维细胞光老化的关键调节因子
DOI：
10.1111/bjd.18410
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发表时间：
2019-10-20
影响因子：
10.3
通讯作者：
Lu, H.
中科院分区：
文献类型：
--
作者：
Lan, Y.;Wang, Y.;Lu, H.
背景慢性紫外线(UV)辐射(主要是UVA)可诱导人皮肤成纤维细胞中基质金属蛋白酶(MMPs)的表达持续增加，尤其是MMP1、MMP2、MMP3和MMP9。MMPs可导致纤维结缔组织的降解，这是导致皮肤光老化的主要原因。成纤维细胞感知UVA并触发参与MMPs上调的细胞信号通路的分子机制尚未很好地阐明。目的研究正常人真皮成纤维细胞(NHDF)中视蛋白(OPN)3的光老化作用及其可能机制。方法采用实时荧光定量聚合酶链式反应和Western印迹分析方法分析OPN3在NHDF和光老化模型中的表达水平。随后，检测UVA照射前后转染OPN3抑制剂和光老化相关指标的NHDF中MMP1、MMP2、MMP3和MMP9的表达水平，以及信号通路蛋白分子的表达情况。结果我们提供了OPN3在NHDF中启动UVA光传导的证据。OPN3通过激活钙/钙调蛋白依赖性蛋白激酶II、环磷酸腺苷反应元件结合蛋白、细胞外信号调节蛋白、c-jun氨基末端蛋白和p38，激活激活蛋白1的磷酸化，最终上调NHDF中MMP1、MMP2、MMP3和MMP9的表达。在这里，我们首次证明OPN3是通过钙依赖的G蛋白偶联信号通路上调UVA暴露后NHDF中MMP1、MMP2、MMP3和MMP9的关键感受器。结论我们的研究为理解人类皮肤细胞对UVA辐射的反应的分子机制提供了洞察力，并可能揭示预防皮肤光老化或临床治疗的分子靶点。
Background Chronic exposure to ultraviolet (UV) radiation (mainly UVA) induces a sustained increase of matrix metalloproteinases (MMPs), especially MMP1, MMP2, MMP3 and MMP9 in human skin fibroblasts. MMPs can lead to the degradation of fibrous connective tissue, which is the main cause of skin photoageing. The molecular mechanisms through which fibroblasts sense UVA and trigger the cell signalling pathways involved in the upregulation of MMPs have not been well elucidated. Objectives Here, we investigated the function and potential mechanisms of photoageing of opsin (OPN)3 in normal human dermal fibroblasts (NHDFs). Methods Real-time polymerase chain reaction and Western blot analysis were used to analyse the expression levels of OPN3 in NHDFs and photoageing models. Subsequently, NHDFs transfected with OPN3 inhibitors and indicators related to photoageing before and after UVA irradiation included expression levels of MMP1, MMP2, MMP3 and MMP9, and signalling pathway protein molecules were examined. Results We provide evidence that OPN3 initiates UVA phototransduction in NHDFs. OPN3 triggers phosphorylation of activator protein 1 and ultimately upregulates MMP1, MMP2, MMP3 and MMP9 in NHDFs through activating Ca2+/calmodulin-dependent protein kinase II, cyclic adenosine monophosphate response element-binding protein, extracellular signal-regulated kinase, c-JUN N-terminal kinase and p38. Here, we demonstrate for the first time that OPN3 is the key sensor responsible for upregulating MMP1, MMP2, MMP3 and MMP9 in NHDFs following UVA exposure via the calcium-dependent G protein-coupled signalling pathway. Conclusions Our studies provide insights into the understanding of the molecular mechanisms through which human skin cells respond to UVA radiation and may reveal molecular targets for skin photoageing prevention or clinical management.