视蛋白3是紫外线A诱导人皮肤成纤维细胞中光老化的关键调节剂。,British Journal of Dermatology

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视蛋白3是紫外线A诱导人皮肤成纤维细胞中光老化的关键调节剂。
British Journal of Dermatology ( IF 11.0 ) Pub Date : 2019-10-20 , DOI: 10.1111/bjd.18410
Y Lan ₁ , Y Wang ₁ , H Lu ₁

Affiliation

背景技术长期暴露于紫外（UV）辐射（主要是UVA）诱导人皮肤成纤维细胞中基质金属蛋白酶（MMP），尤其是MMP1，MMP2，MMP3和MMP9的持续增加。MMP可导致纤维结缔组织降解，这是皮肤光老化的主要原因。成纤维细胞通过其感知UVA并触发MMPs上调所涉及的细胞信号通路的分子机制尚未得到很好的阐明。目的在这里，我们调查了正常人皮肤成纤维细胞（NHDFs）中视蛋白（OPN）3的光老化的功能和潜在机制。方法采用实时聚合酶链反应和Western blot方法分析OPN3在NHDFs和光老化模型中的表达水平。后来，用OPN3抑制剂和与UVA照射前后的光老化相关的指示剂转染的NHDF包括MMP1，MMP2，MMP3和MMP9的表达水平，并检查了信号通路蛋白分子。结果我们提供了证据，表明OPN3可在NHDF中引发UVA光转导。OPN3通过激活Ca2 + /钙调蛋白依赖性蛋白激酶II，环状单磷酸腺苷反应元件结合蛋白，细胞外信号调节激酶，c-JUN N-来激活蛋白1的磷酸化并最终上调NHDF中的MMP1，MMP2，MMP3和MMP9。末端激酶和p38。在这里，我们首次证明了OPN3是负责通过钙依赖性G蛋白偶联信号传导途径暴露于UVA后上调NHDFs中MMP1，MMP2，MMP3和MMP9的关键传感器。结论我们的研究为深入理解人类皮肤细胞对UVA辐射的分子机制提供了见解，并可能揭示了预防皮肤光老化或临床管理的分子靶标。关于此主题的已知信息是什么？光老化的成纤维细胞会随着长期的紫外线（UV）照射而积累。基质金属蛋白酶（MMP）在光老化的发病机理中起重要作用。MMP1，MMP2，MMP3和MMP9负责破坏严重光损伤的皮肤中的成纤维细胞胶原蛋白。视蛋白（OPNs）是七螺旋G蛋白偶联受体超家族的光敏成员，该家族是一系列细胞表面受体，可通过多种刺激激活并介导跨膜信号传导。这项研究增加了什么？OPN3在成纤维细胞中高度表达，对UVA辐射有反应。OPN3通过钙依赖性G蛋白偶联的信号通路调节MMP1，MMP2，MMP3和MMP9的表达。OPN3是一种光敏传感器，在皮肤的光老化过程中起着重要的作用。

"点击查看英文标题和摘要"

Opsin 3 is a key regulator of ultraviolet A-induced photoageing in human dermal fibroblast cells.

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. What's already known about this topic? Photoaged fibroblasts accumulate with long-term ultraviolet (UV) exposure. Matrix metalloproteinases (MMPs) play an important role in the pathogenesis of photoageing. MMP1, MMP2, MMP3 and MMP9 are responsible for the destruction of fibroblast collagen in severely photodamaged skin. Opsins (OPNs) are light-sensitive members of the superfamily of heptahelical G protein-coupled receptors, a family of cell surface receptors that are activated by a variety of stimuli and mediate signalling across membranes. What does this study add? OPN3 is highly expressed in fibroblasts and responds to UVA irradiation. OPN3 regulates the expression of MMP1, MMP2, MMP3 and MMP9 via the calcium-dependent G protein-coupled signalling pathway. OPN3 is a light-sensitive sensor that plays an important role in photoageing of the skin.

更新日期：2019-10-20

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