Genomic characterization of a three-dimensional skin model following exposure to ionizing radiation.
Genomic characterization of a three-dimensional skin model following exposure to ionizing radiation.
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DOI：
10.1093/jrr/rrs063
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发表时间：
2012-11-01
影响因子：
2
通讯作者：
Rocke DM
中科院分区：
文献类型：
--
作者：
Yunis R;Albrecht H;Kalanetra KM;Wu S;Rocke DM
本研究旨在表征三维（3D）皮肤模型中对低剂量与中等剂量电离辐射（LIPE与MIPE）的基因组反应，该模型显示出比单层细胞培养物更接近人类皮肤的组织复杂性。将EpiDermFT皮片暴露于0、0.1和1戈伊剂量的X射线，并在照射后5分钟、3、8和24小时（IR后）收获。询问RNA的整体基因表达改变。我们的研究结果表明，与Leptin相比，Meptin在24小时内调节了更多的基因。然而，立即和整个第一个3小时后，IR，LIFE调制更多的基因比MIFE，主要与细胞-细胞信号和生存促进。仅在IR后3小时在Mesenchymal中检测到显著的通路调节，并诱导促进细胞凋亡的基因。总的来说，这些数据显示了对Leptin与Meptin的反应的不同动态，特别是在细胞周期分布方面。LDIR暴露的组织表现出的迹象，试图细胞周期重新进入早在3小时后IR，但超过8小时，在G1/S检查点被逮捕。24 h时，细胞似乎在G2/M检查点聚集。MDIR暴露的组织没有表现出延长的G1/S期阻滞，而是延长的G2/M期阻滞，至少持续24 h。到24小时细胞表现出的迹象，在两个LIFE和MDIR暴露的组织中的恢复。总之，对Leptin与Meptin的初始细胞应答中最显著的差异是Leptin中保护和存活的促进与Meptin中凋亡的促进。
This study aimed at characterizing the genomic response to low versus moderate doses of ionizing radiation (LDIR versus MDIR) in a three-dimensional (3D) skin model, which exhibits a closer tissue complexity to human skin than monolayer cell cultures. EpiDermFT skin plugs were exposed to 0, 0.1 and 1 Gy doses of X-rays and harvested at 5 min, 3, 8 and 24 h post-irradiation (post-IR). RNA was interrogated for global gene expression alteration. Our results show that MDIR modulated a larger number of genes over the course of 24 h compared to LDIR. However, immediately and throughout the first 3h post-IR, LDIR modulated a larger number of genes than MDIR, mostly associated with cell–cell signaling and survival promotion. Significant modulation of pathways was detected only at 3 h post-IR in MDIR with induction of genes promoting apoptosis. Collectively, the data show different dynamics in the response to LDIR versus MDIR, especially in cell-cycle distribution. LDIR-exposed tissues showed signs of attempted cell-cycle re-entry as early as 3 h post-IR, but were arrested beyond 8 h at the G1/S checkpoint. At 24 h, cells appeared to accumulate at the G2/M checkpoint. MDIR-exposed tissues did not exhibit a prolonged G1/S arrest but rather a prolonged G2/M arrest, which was sustained at least up to 24 h. By 24 h cells exhibited signs of recovery in both LDIR- and MDIR-exposed tissues. In summary, the most pronounced difference in the initial cellular response to LDIR versus MDIR is the promotion of protection and survival in LDIR versus the promotion of apoptosis in MDIR.
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影响因子：
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