褪黑激素通过人皮肤成纤维细胞中的 JNK/AP-1 信号通路抑制氧化损伤和 MMP 表达来防止 UVB 诱导的皮肤光老化,Life

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褪黑激素通过人皮肤成纤维细胞中的 JNK/AP-1 信号通路抑制氧化损伤和 MMP 表达来防止 UVB 诱导的皮肤光老化
Life ( IF 2.991 ) Pub Date : 2022-06-24 , DOI: 10.3390/life12070950
Mehtap Yuksel Egrilmez ₁ , Semra Kocturk ₂ , Sebnem Aktan ₃ , Gulgun Oktay ₂ , Halil Resmi ₂ , Hatice Simsek Keskin ₄ , Gul Guner Akdogan _{2,

5} , Sebnem Ozkan ₃

Affiliation

暴露于紫外线 (UV) 照射会对皮肤造成损害并诱发光老化。紫外线照射会刺激活性氧/氮物质的产生，从而导致成纤维细胞中表皮生长因子受体 (EGFR) 和丝裂原活化蛋白激酶 (MAPK) 的激活。MAPK 负责激活激活蛋白 1 (AP-1)，随后上调基质金属蛋白酶 (MMP) 的表达。褪黑激素是一种有效的自由基清除剂，已知具有光保护作用。本研究的目的是研究褪黑激素在 UVB 照射的原代人真皮成纤维细胞 (HDF) 中的光保护作用的潜在分子机制，包括 EGFR 活化、氧化/亚硝化损伤、JNK/AP-1 活化、MMP 活性、以及金属蛋白酶-1 (TIMP-1) 和 I 型前胶原 (PIP-C) 组织抑制剂的水平。在这项研究中，HDF 用 1 μM 褪黑激素预处理，然后用 0.1 J/cm 照射² UVB。在不同时间点分析分子的变化。褪黑激素通过降低丙二醛、氧化/还原谷胱甘肽和硝基酪氨酸的比例来抑制 UVB 诱导的氧化/亚硝化应激损伤。褪黑激素下调紫外线诱导的 EGFR 活化和 JNK/AP-1 信号通路。UVB 诱导的 MMP-1 和 MMP-3 活性降低，而 TIMP-1 和 PIP-C 的水平因褪黑激素而增加。这些发现表明，褪黑激素可以通过抑制 MMP-1 和 MMP-3 活性以及增加 TIMP-1 和 PIP-C 水平来防止 UVB 辐射的不利影响，可能是通过抑制氧化/亚硝化损伤、EGFR 和 JNK/ HDF 中的 AP-1 激活。

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Melatonin Prevents UVB-Induced Skin Photoaging by Inhibiting Oxidative Damage and MMP Expression through JNK/AP-1 Signaling Pathway in Human Dermal Fibroblasts

Exposure to ultraviolet (UV) irradiation causes damage to the skin and induces photoaging. UV irradiation stimulates production of reactive oxygen/nitrogen species, which results in activation of epidermal growth factor receptor (EGFR) and mitogen-activated protein kinases (MAPK) in fibroblasts. MAPKs are responsible for activation of activator protein-1 (AP-1), which subsequently upregulates expression of matrix metalloproteinases (MMPs). Melatonin is a potent free radical scavenger which is known to have photoprotective effects. The aim of this study is to investigate the underlying molecular mechanisms for the photoprotective effects of melatonin in UVB-irradiated primary human dermal fibroblasts (HDFs) in terms of EGFR activation, oxidative/nitrosative damage, JNK/AP-1 activation, MMP activities, and the levels of tissue inhibitors of metalloproteinase-1 (TIMP-1) and type I procollagen (PIP-C). In this study, HDFs were pretreated with 1 μM of melatonin and then irradiated with 0.1 J/cm² of UVB. Changes in the molecules were analyzed at different time points. Melatonin inhibited UVB-induced oxidative/nitrosative stress damage by reducing malondialdehyde, the ratio of oxidized/reduced glutathione, and nitrotyrosine. Melatonin downregulated UV-induced activation of EGFR and the JNK/AP-1 signaling pathway. UVB-induced activities of MMP-1 and MMP-3 were decreased and levels of TIMP-1 and PIP-C were increased by melatonin. These findings suggest that melatonin can protect against the adverse effects of UVB radiation by inhibiting MMP-1 and MMP-3 activity and increasing TIMP-1 and PIP-C levels, probably through the suppression of oxidative/nitrosative damage, EGFR, and JNK/AP-1 activation in HDFs.

更新日期：2022-06-25

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