The dynamic cellular and molecular features during the development of radiation proctitis revealed by transcriptomic profiling in mice.
The dynamic cellular and molecular features during the development of radiation proctitis revealed by transcriptomic profiling in mice.
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通过小鼠转录组分析揭示放射性直肠炎发展过程中的动态细胞和分子特征
DOI：
10.1186/s12864-022-08668-5
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发表时间：
2022-06-09
期刊：
影响因子：
4.4
通讯作者：
中科院分区：
文献类型：
--
作者：
放射性直肠炎是盆腔肿瘤放射治疗最常见的并发症。目前缺乏有效的临床治疗方法，其潜在机制也知之甚少。本研究旨在利用小鼠模型，从RNomics的角度动态揭示RP进展的机制，为RP的合理治疗策略提供帮助。给予小鼠单剂量25戈伊直肠照射，并在照射后4小时、1天、3天、2周和8周（PI）取出直肠组织用于组织病理学评估和RNA-seq分析。根据组织病理学特点，将RP动物模型的发展过程分为急性期（感染后4 h、1 d和3 d）、亚急性期（感染后2周）和慢性期（感染后8周），可概括人RP不同阶段的特点。对RNA-seq数据的生物信息学分析表明，在辐射后急性损伤期，改变的基因主要富集在DNA损伤反应、p53信号通路和代谢变化方面;而在组织重建的亚急性和慢性阶段，参与血管发育、细胞外基质组织化、炎症和免疫反应等生物学过程的基因出现失调。我们进一步确定了枢纽基因在最重要的生物过程中，在每个时间点使用蛋白质-蛋白质相互作用分析，并验证了这些基因的差异表达的定量实时PCR分析。我们的研究揭示了RP发生发展过程中的分子事件，为设计针对RP不同发展阶段的药物提供了分子基础。在线版本包含补充材料，可通过10.1186/s12864-022-08668-5获得。
Radiation proctitis (RP) is the most common complication of radiotherapy for pelvic tumor. Currently there is a lack of effective clinical treatment and its underlying mechanism is poorly understood. In this study, we aimed to dynamically reveal the mechanism of RP progression from the perspective of RNomics using a mouse model, so as to help develop reasonable therapeutic strategies for RP. Mice were delivered a single dose of 25 Gy rectal irradiation, and the rectal tissues were removed at 4 h, 1 day, 3 days, 2 weeks and 8 weeks post-irradiation (PI) for both histopathological assessment and RNA-seq analysis. According to the histopathological characteristics, we divided the development process of our RP animal model into three stages: acute (4 h, 1 day and 3 days PI), subacute (2 weeks PI) and chronic (8 weeks PI), which could recapitulate the features of different stages of human RP. Bioinformatics analysis of the RNA-seq data showed that in the acute injury period after radiation, the altered genes were mainly enriched in DNA damage response, p53 signaling pathway and metabolic changes; while in the subacute and chronic stages of tissue reconstruction, genes involved in the biological processes of vessel development, extracellular matrix organization, inflammatory and immune responses were dysregulated. We further identified the hub genes in the most significant biological process at each time point using protein-protein interaction analysis and verified the differential expression of these genes by quantitative real-time-PCR analysis. Our study reveals the molecular events sequentially occurred during the course of RP development and might provide molecular basis for designing drugs targeting different stages of RP development. The online version contains supplementary material available at 10.1186/s12864-022-08668-5.
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DOI：
10.1080/13510002.2017.1416773
发表时间：
2018-12
期刊：
Redox report : communications in free radical research
影响因子：
--
作者：
Beyfuss K;Hood DA
通讯作者：
Hood DA
影响因子：
5.7
作者：
LANGBERG, CW;HAUERJENSEN, M;KANE, CJM
通讯作者：
KANE, CJM
影响因子：
2.8
作者：
Abayomi, J.;Kirwan, J.;Hackett, A.
通讯作者：
Hackett, A.
影响因子：
4.6
作者：
Karamanolis G;Delladetsima I;Kouloulias V;Papaxoinis K;Panayiotides I;Haldeopoulos D;Triantafyllou K;Kelekis N;Ladas SD
通讯作者：
Ladas SD
影响因子：
11.5
作者：
Haydont, Valrie;Bourgier, Celine;Vozenin-Brotons, Marie-Catherine
通讯作者：
Vozenin-Brotons, Marie-Catherine