Department of Gastroenterology and Hepatology, Graduate School of Medicine, Yamaguchi University, Minami Kogushi 1-1-1, Ube 755-8505, Japan.
Department of Environmental Oncology, Institute of Industrial Ecological Sciences, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu 807-8555, Japan.
Int J Mol Sci. 2022 Jul 4;23(13):7429. doi: 10.3390/ijms23137429.
In recent years, research has been conducted to develop new medical treatments by simulating environments existing in space, such as zero-gravity. In this study, we evaluated the cell proliferation and gene expression of activated primary human hepatic stellate cells (HHSteCs) under simulated microgravity (SMG). Under SMG, cell proliferation was slower than in 1 G, and the evaluation of gene expression changes on day 1 of SMG by serial analysis of gene expression revealed the presence of Sirtuin, EIF2 signaling, hippo signaling, and epithelial adherence junction signaling. Moreover, reactive oxygen species were upregulated under SMG, and when N-acetyl-cystein was added, no difference in proliferation between SMG and 1 G was observed, suggesting that the oxidative stress generated by mitochondrial dysfunction caused a decrease in proliferation. Upstream regulators such as smad3, NFkB, and FN were activated, and cell-permeable inhibitors such as Ly294002 and U0126 were inhibited. Immunohistochemistry performed to evaluate cytoskeletal changes showed that more β-actin was localized in the cortical layer under SMG.
近年来，人们一直在研究通过模拟太空中存在的环境（如微重力）来开发新的医疗方法。在这项研究中，我们评估了模拟微重力（SMG）下激活的原代人肝星状细胞（HHSteCs）的细胞增殖和基因表达。在 SMG 下，细胞增殖比 1G 时慢，通过基因表达系列分析（SAGE）在 SMG 第 1 天评估基因表达变化，发现存在 Sirtuin、EIF2 信号、Hippo 信号和上皮细胞粘附连接信号。此外，SMG 下活性氧（ROS）上调，当添加 N-乙酰半胱氨酸（NAC）时，SMG 和 1G 之间的增殖没有差异，表明线粒体功能障碍产生的氧化应激导致增殖减少。上游调节剂如 smad3、NFkB 和 FN 被激活，细胞通透性抑制剂如 Ly294002 和 U0126 被抑制。为评估细胞骨架变化而进行的免疫组织化学显示，SMG 下更多的β-肌动蛋白定位于皮质层。
