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Differential gene regulation under altered gravity conditions in follicular thyroid cancer cells: Relationship between the extracellular matrix and the cytoskeleton

机译:滤泡甲状腺癌细胞在重力条件下的差异基因调控:细胞外基质与细胞骨架之间的关系

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Extracellular matrix proteins, adhesion molecules, and cytoskeletal proteins form a dynamic network interacting with signalling molecules as an adaptive response to altered gravity. An important issue is the exact differentiation between real microgravity responses of the cells or cellular reactions to hypergravity and/or vibrations. To determine the effects of real microgravity on human cells, we used four DLR parabolic flight campaigns and focused on the effects of short-term microgravity (22 s), hypergravity (1.8 g), and vibrations on ML-1 thyroid cancer cells. No signs of apoptosis or necrosis were detectable. Gene array analysis revealed 2430 significantly changed transcripts. After 22 s microgravity, the F-actin and cytokeratin cytoskeleton was altered, and ACTB and KRT80 mRNAs were significantly upregulated after the first and thirty-first parabolas. The COL4A5 mRNA was downregulated under microgravity, whereas OPN and FN were significantly upregulated. Hypergravity and vibrations did not change ACTB, KRT-80 or COL4A5 mRNA. MTSS1 and LIMA1 mRNAs were downregulated/slightly upregulated under microgravity, upregulated in hypergravity and unchanged by vibrations. These data indicate that the graviresponse of ML-1 cells occurred very early, within the first few seconds. Downregulated MTSS1 and upregulated LIMA1 may be an adaptive mechanism of human cells for stabilizing the cytoskeleton under microgravity conditions.
机译:细胞外基质蛋白,粘附分子和细胞骨架蛋白形成动态网络,与信号分子相互作用,作为对重力变化的适应性反应。一个重要的问题是细胞的实际微重力反应或细胞对超重力和/或振动的反应之间的确切区别。为了确定实际微重力对人体细胞的影响,我们使用了四次DLR抛物线飞行运动,重点研究了短期微重力(22 s),超重力(1.8 g)和振动对ML-1甲状腺癌细胞的影响。没有检测到凋亡或坏死的迹象。基因阵列分析显示2430个显着改变的转录本。在微重力作用下,经过第一个抛物线和第三十一个抛物线后,F-肌动蛋白和细胞角蛋白的细胞骨架发生改变,并且ACTB和KRT80 mRNA显着上调。在微重力下,COL4A5 mRNA被下调,而OPN和FN被显着上调。超重力和振动不会改变ACTB,KRT-80或COL4A5 mRNA。 MTSS1和LIMA1 mRNA在微重力下被下调/略微上调,在超重力下上调,并且在振动下未发生变化。这些数据表明,ML-1细胞的重力反应很早就发生在最初的几秒钟内。 MTSS1的下调和LIMA1的上调可能是人类细胞在微重力条件下稳定细胞骨架的一种适应机制。

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