Nrf2 null enhances UVB-induced skin inflammation and extracellular matrix damages.
Nrf2 null enhances UVB-induced skin inflammation and extracellular matrix damages.
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DOI：
10.1186/2045-3701-4-39
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发表时间：
2014
影响因子：
7.5
通讯作者：
Kong AN
中科院分区：
文献类型：
--
作者：
Saw CL;Yang AY;Huang MT;Liu Y;Lee JH;Khor TO;Su ZY;Shu L;Lu Y;Conney AH;Kong AN
nrf 2在防御氧化应激和炎症中起着关键作用。我们先前报道了Nrf 2赋予对紫外线B（UVB）诱导的炎症、晒伤反应的保护，并且参与萝卜硫素介导的皮肤光保护作用。在这项研究中，我们的目的是证明Nrf 2对炎症介导的细胞外基质（ECM）损伤的UVB辐射诱导的保护作用。UVB照射后一周，Nrf 2野生型（Nrf 2 WT）和敲除（Nrf 2 KO）小鼠的耳活检重量均显著增加。然而，与WT小鼠相比，KO小鼠的这些重量增加更显著，表明KO小鼠的炎症反应更强。此外，我们分析了许多标志物的蛋白质表达，包括巨噬细胞炎症蛋白-2（MIP-2）、基质金属蛋白酶原-9（MMP-9）和p53。p53是DNA修复的调节因子，在Nrf 2 KO小鼠中过表达，表明Nrf 2的缺失导致更持续的DNA损伤。与UVB照射的WT小鼠相比，UVB照射的Nrf 2 KO小鼠中的ECM降解和炎症增加也更显著。此外，Nrf 2对UVB照射的保护作用是通过增加HO-1蛋白表达介导的。总的来说，我们的研究结果表明，Nrf 2在保护免受UVB照射中起着关键作用，并且Nrf 2的光保护作用与抑制ECM降解和炎症密切相关。
Nrf2 plays a critical role in defending against oxidative stress and inflammation. We previously reported that Nrf2 confers protection against ultraviolet-B (UVB)-induced inflammation, sunburn reaction, and is involved in sulforaphane-mediated photo-protective effects in the skin. In this study, we aimed to demonstrate the protective role of Nrf2 against inflammation-mediated extracellular matrix (ECM) damage induced by UVB irradiation. Ear biopsy weights were significantly increased in both Nrf2 wild-type (Nrf2 WT) and knockout (Nrf2 KO) mice one week after UVB irradiation. However, these weights increased more significantly in KO mice compared to WT mice, suggesting a greater inflammatory response in KO mice. In addition, we analyzed the protein expression of numerous markers, including macrophage inflammatory protein-2 (MIP-2), pro-matrix metalloproteinase-9 (MMP-9), and p53. p53, a regulator of DNA repair, was overexpressed in Nrf2 KO mice, indicating that the absence of Nrf2 led to more sustained DNA damage. There was also more substantial ECM degradation and increased inflammation in UVB-irradiated Nrf2 KO mice compared to UVB-irradiated WT mice. Furthermore, the protective effects of Nrf2 in response to UVB irradiation were mediated by increased HO-1 protein expression. Collectively, our results show that Nrf2 plays a key role in protecting against UVB irradiation and that the photo-protective effect of Nrf2 is closely related to the inhibition of ECM degradation and inflammation.
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影响因子：
7.4
作者：
Reuter, Simone;Gupta, Subash C.;Chaturvedi, Madan M.;Aggarwal, Bharat B.
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