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低剂量率照射诱导的小鼠肠内 G6PC2 和 MUC6 可能与炎症性肠病有关。

Possible association of G6PC2 and MUC6 induced by low‑dose‑rate irradiation in mouse intestine with inflammatory bowel disease.

机构信息

College of Veterinary Medicine and BK21 FOUR Program, Chonnam National University, Gwangju 61186, Republic of Korea.

Department of Anatomy and Convergence Medical Science, College of Medicine, Institute of Health Sciences, Gyeongsang National University, Jinju, South Gyeongsangnam-do 52727, Republic of Korea.

出版信息

Mol Med Rep. 2024 Jul;30(1). doi: 10.3892/mmr.2024.13251. Epub 2024 May 24.

Abstract

Although there are several types of radiation exposure, it is debated whether low‑dose‑rate (LDR) irradiation (IR) affects the body. Since the small intestine is a radiation‑sensitive organ, the present study aimed to evaluate how it changes when exposed to LDR IR and identify the genes sensitive to these doses. After undergoing LDR (6.0 mGy/h) γ radiation exposure, intestinal RNA from BALB/c mice was extracted 1 and 24 h later. Mouse whole genome microarrays were used to explore radiation‑induced transcriptional alterations. Reverse transcription‑quantitative (RT‑q) PCR was used to examine time‑ and dose‑dependent radiation responses. The histopathological status of the jejunum in the radiated mouse was not changed by 10 mGy of LDR IR; however, 23 genes were upregulated in response to LDR IR of the jejunum in mice after 1 and 24 h of exposure. Upregulated genes were selected to validate the results of the RNA sequencing analysis for RT‑qPCR detection and results showed that only Na/K transporting subunit α4, glucose‑6‑phosphatase catalytic subunit 2 (G6PC2), mucin 6 (MUC6) and transient receptor potential cation channel subfamily V member 6 levels significantly increased after 24 h of LDR IR. Furthermore, G6PC2 and MUC6 were notable genes induced by LDR IR exposure according to protein expression via western blot analysis. The mRNA levels of G6PC2 and MUC6 were significantly elevated within 24 h under three conditions: i) Exposure to LDR IR, ii) repeated exposure to LDR IR and iii) exposure to LDR IR in the presence of inflammatory bowel disease. These results could contribute to an improved understanding of immediate radiation reactions and biomarker development to identify radiation‑susceptible individuals before histopathological changes become noticeable. However, further investigation into the specific mechanisms involving G6PC2 and MUC6 is required to accomplish this.

摘要

尽管存在几种类型的辐射暴露,但低剂量率(LDR)辐照(IR)是否会影响身体仍存在争议。由于小肠是一种对辐射敏感的器官,本研究旨在评估其在暴露于 LDR IR 时如何变化,并确定对这些剂量敏感的基因。在接受 LDR(6.0 mGy/h)γ 辐射暴露后,1 小时和 24 小时后从 BALB/c 小鼠中提取肠 RNA。使用小鼠全基因组微阵列来探索辐射诱导的转录变化。逆转录定量(RT-q)PCR 用于检查时间和剂量依赖性的辐射反应。10 mGy 的 LDR IR 不会改变辐射小鼠空肠的组织病理学状态;然而,在暴露于 LDR IR 1 和 24 小时后,23 个基因在小鼠空肠中上调。选择上调基因以验证 RNA 测序分析的结果进行 RT-qPCR 检测,结果表明仅 Na/K 转运亚基α4、葡萄糖-6-磷酸酶催化亚基 2(G6PC2)、粘蛋白 6(MUC6)和瞬时受体电位阳离子通道亚家族 V 成员 6 的水平在 LDR IR 后 24 小时显著增加。此外,根据蛋白质表达通过 western blot 分析,G6PC2 和 MUC6 是 LDR IR 暴露诱导的显著基因。在三种条件下:i)暴露于 LDR IR,ii)重复暴露于 LDR IR 和 iii)在炎症性肠病存在下暴露于 LDR IR,G6PC2 和 MUC6 的 mRNA 水平在 24 小时内显著升高。这些结果有助于更好地理解即时辐射反应和生物标志物的开发,以在组织病理学变化变得明显之前识别辐射敏感个体。然而,需要进一步研究涉及 G6PC2 和 MUC6 的具体机制来实现这一目标。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/424c/11134309/1d2eb50f725f/mmr-30-01-13251-g00.jpg

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