School of Biosystems and Biomedical Sciences, College of Health Science, Korea University, 145 Anam-ro, Seongbuk-gu, Seoul, 02841, Republic of Korea.
School of Biomedical Engineering, College of Health Science, Korea University, 145 Anam-ro, Seongbuk-gu, Seoul, 02841, Republic of Korea.
Biochem Biophys Res Commun. 2019 Oct 15;518(2):388-395. doi: 10.1016/j.bbrc.2019.08.068. Epub 2019 Aug 14.
UV-induced skin damage is involved in ROS overproduction and the overexpression of matrix metalloproteinases (MMPs), which are inhibited by TIMPs (tissue inhibitor of neural stem cells (NSCs)). These proteins may be associated with skin regeneration through the activation of TIMP proteins, but there have been no reports of treatment of skin photodamage using NSCs and their secreted proteins TIMP-1 and TIMP-2. Here we investigated the photoprotective role of NSCs and their TIMP proteins for the inhibition of UVB-irradiation damage in fibroblasts in SKH-1 mice. SKH-1 hairless mice were divided into three groups (n = 4 per group): normal, treatment, and control groups. The latter two groups were dorsally exposed to UVB irradiation for 12 weeks. After UVB irradiation, treatments with NSC-CM and its secreted factors TIMP-1 and TIMP-2, markedly ameliorated the photodamage triggered by the increase in MMP expression and activity through ROS production, and the subsequent activation of the NF-κB pathway in UVB-irradiated fibroblasts and the treatment mouse group. In addition, the topical application of NSC-CM to mice in the treatment group after irradiation clearly inhibited the expression of γ-H2AX, a DNA damage marker, through the activation of the DNA repair enzyme Rad50. These results demonstrate that NSC-CM or TIMPs proteins can ameliorate skin photodamage induced by UVB-irradiation in in vitro and in vivo systems.
UV 诱导的皮肤损伤涉及 ROS 的过度产生和基质金属蛋白酶 (MMPs) 的过度表达，而 TIMPs（神经干细胞 (NSC) 的组织抑制剂）可以抑制 MMPs。这些蛋白质可能通过 TIMP 蛋白的激活与皮肤再生有关，但尚未有报道使用 NSCs 及其分泌蛋白 TIMP-1 和 TIMP-2 治疗皮肤光损伤。在这里，我们研究了 NSCs 及其 TIMP 蛋白在抑制 SKH-1 小鼠成纤维细胞中 UVB 照射损伤中的光保护作用。将 SKH-1 无毛小鼠分为三组（每组 n=4）：正常组、治疗组和对照组。后两组背部接受 UVB 照射 12 周。在 UVB 照射后，用 NSC-CM 及其分泌因子 TIMP-1 和 TIMP-2 处理，通过 ROS 产生和随后 NF-κB 途径的激活，显著改善 MMP 表达和活性增加引起的光损伤，以及 UVB 照射的成纤维细胞和治疗组小鼠中的损伤。此外，在照射后将 NSC-CM 局部应用于治疗组小鼠，通过激活 DNA 修复酶 Rad50 明显抑制了 γ-H2AX（一种 DNA 损伤标志物）的表达。这些结果表明，NSC-CM 或 TIMP 蛋白可以改善体外和体内系统中由 UVB 照射引起的皮肤光损伤。
