脱氧雪腐镰刀菌烯醇致小鼠畸形骨骼组织差异表达基因及相关通路分析

doi:10.3969/j.issn.1004-616x.2015.01.001

癌变·畸变·突变

• 论著 • 下一篇

脱氧雪腐镰刀菌烯醇致小鼠畸形骨骼组织差异表达基因及相关通路分析

李岩，赵英会，庄东明，李晓霞，于爱莲^*

泰山医学院基础医学院，山东泰安 271000

收稿日期:2014-05-11 修回日期:2014-01-06 出版日期:2015-01-31 发布日期:2015-01-31
通讯作者: 于爱莲，E-mail： alyu@tsmc.edu.cn
作者简介:李岩，E-mail：liyan2313935@163.com
基金资助:
山东省科技攻关项目(2007GG30002016)；国家传染病重大专项合作项目(2009ZX10004-216)；山东省自然科学基金(ZR2013HL060)

Differential gene expression and related pathways of skeletal malformations induced by deoxynivalenol in mice

LI Yan，ZHAO Yinghui，ZHUANG Dongming，LI Xiaoxia，YU Ailian^*

School of Basic Medicine Sciences, Taishan Medical University, Tai’an 271000, Shandong, China

Received:2014-05-11 Revised:2014-01-06 Online:2015-01-31 Published:2015-01-31

摘要/Abstract

摘要：

目的：筛选脱氧雪腐镰刀菌烯醇(DON)致小鼠胚胎畸形骨骼组织的差异表达基因及相关信号传导通路，从基因水平上阐明DON致小鼠骨骼畸形的分子基础。方法：取孕期小鼠30只，随机分成3个不同浓度DON染毒组、溶剂对照组和空白对照组，每组6只，将DON染毒组孕鼠于孕期第7～10天连续腹腔注射DON，染毒后第18天麻醉剖腹取出胎鼠骨骼组织，提取椎骨骨骼组织总RNA，通过反转录法获取畸形骨骼组织和正常对照组骨骼组织的cDNA，并对其分别进行荧光标记，采用全基因组芯片技术对小鼠胚胎畸形骨骼组织与正常对照组织的差异基因表达谱进行分析，采用基因本体学分析软件对差异表达基因进行功能分析，DAVID database数据库筛选差异表达基因涉及的信号通路，并利用荧光定量PCR(qPCR)技术对基因芯片结果进行验证。结果：在DON染毒组小鼠全基因组芯片上筛选出差异基因282个，其中下调148个，上调134个；在差异表达基因分析的基础上，发现差异表达基因涉及到的通路有153个。qPCR结果表明，上调基因Fbn1、Co19a2、Papss2、Pax1F和下调基因Runx2、Pthlh等6个差异表达基因的相对定量结果与基因芯片检验结果表达趋势一致。结论：应用基因表达谱芯片初步筛选出DON所致胎鼠畸形骨骼与正常胎鼠骨骼组织中的差异表达基因，并通过通路分析发现，上述差异表达基因涉及多条信号传导通路。

关键词: 脱氧雪腐镰刀菌烯醇, 骨骼畸形, 基因芯片, 差异表达基因, 传导通路

Abstract:

OBJECTIVE: To screen the differential gene expression and related pathways of fetal skeletal malformations induced by deoxynivalenol(DON) in mice，and to explore the mechanism of deformities induced by DON at the molecular level. METHODS：30 pregnant mice were randomly divided into 3 experimental groups and 2 control groups，6 in each group. DON injection was performed from days 7 to 10 of pregnancy by intraperitoneal injection into pregnant mice. At GD 18，all mice were killed under isoflurane anesthesia，and vertebral bone tissue of fetuses were collected. Total RNA of vertebral bone tissues was extracted and cDNA was obtained by RT-PCR. Using whole genome microarray technology，the gene expression profiles and the pathways of the rat vertebral bone tissue were studied. Analysis of the function of differentially expressed genes was performed by using software of gene ontology. Screening signaling pathways of differentially expressed genes was done by DAVID database. The results were verified by fluorescence quantitative PCR(qPCR) technology. RESULTS：Microarray analysis showed that 282 genes，including 148 down-regulated and 134 up-regulated genes，were abnormally expressed in fetal vertebral bones after maternal DON exposure. 153 pathways were related to the differentially expressed genes. The relative quantitative results of qPCR were consistent with the results of gene chip test in Fbn1，Co19a2，Papss2， Pax1，Runx2 and Pthlh genes. CONCLUSION： There were differential gene expressions in deformed fetal skeleton between deoxynivalenol-treated rats and normal rats， involving multiple signaling pathways. The differentially expressed genes and signaling pathways may be related to the molecular mechanisms of deformities induced by DON.

Key words: deoxynivalenol, skeletal deformities, gene chip, differentially expressed genes, signaling pathways

李岩，赵英会，庄东明，李晓霞，于爱莲. 脱氧雪腐镰刀菌烯醇致小鼠畸形骨骼组织差异表达基因及相关通路分析[J]. 癌变·畸变·突变, doi: 10.3969/j.issn.1004-616x.2015.01.001.

LI Yan，ZHAO Yinghui，ZHUANG Dongming，LI Xiaoxia，YU Ailian. Differential gene expression and related pathways of skeletal malformations induced by deoxynivalenol in mice[J]. Carcinogenesis, Teratogenesis & Mutagenesis, doi: 10.3969/j.issn.1004-616x.2015.01.001.

参考文献

[1] Moon Y，Kim HK，Suh H，et al. Toxic alterations in chick embryonic liver and spleen by acute exposure to Fusarium-producing mycotoxin deoxynivalenol[J]. Biol Pharm Bull， 2007，30(9)：1808-1812.

[2] Debouck C，Haubruge E，Bollaerts P，et al. Skeletal deformities induced by the intraperitoneal administration of deoxynivalenol(vomitoxin) in mice[J]. Int Orthop，2001， 25(3)： 194-198 .

[3] Collins TF，Sprando RL，Black TN，et al. Effects of deoxynivalenol (DON，vomitoxin) on in utero development in rats[J]. Food Chem Toxicol，2006，44(4)：747-757

[4] Sergeev IN，Kravchenko LV，Piliia NM，et al. The effect of the trichothecene mycotoxin deoxynivalenol (vomitoxin) on calcium homeostasis，vitamin D metabolism and receptors in rats[J]. Vopr Med Khim，1990，36(5)：26-29.

[5] 邓红文，刘耀中. 骨生物学前沿[M]. 北京：高等教育出版社，2006：14.

[6] 刘忠厚. 骨矿与临床[M]. 北京：中国科技出版社，2006：3.

[7] 刘秀芳，张爱华，张红英，等. 脱氧雪腐镰刀菌烯醇诱导血管内皮细胞凋亡及其凋亡相关因子的初步研究[J]. 畜牧兽医学报，2008，39(6)：778-783.

[8] 王秀，王蔚，王义权. Pax 基因功能及其选择性剪接的研究进展[J]. 生命科学，2008，20(1)：125-130.

[9] Enomoto H，Furuichi T，Zanma A，et al. RUNX2 deficiency in chondrocytes causes radiogenic changes in vitro[J]. J Cell Sci，2004，117(Sup 3)：417-425.

[10] Takeda S，Bonnamy JP，Owen MJ，et al. Continuous expression of CBFα1 in nonhypertrophic chondrocytes uncovers its ability to induce hypertrophic chondrocyte differentiation and partially rescues CBFα1-deficientmice[J]. Genes Dev，2001， 15(4)：467-481.

[11] Rauch DA，Hurchla MA，Harding JC，et al. The ARF tumor suppressor regulates bone remodeling and osteosarcoma develop- ment in mice[J]. PLoS One，2010，5(12)： e15755.

[12] 伍力，尹杰，冯泽猛，等. 脱氧雪腐镰刀菌烯醇毒理作用研究进展[J]. 生态毒理学报，2013，8(3)：331-337.

[13] Hsieh SC，Chen NT，Lo SH. Conditional loss of PTEN leads to skeletal abnormalities and lipoma formation[J]. Mol Carcinog， 2009，48(6)：545-552.

[14] 陈小静，高艳虹. Wnt信号通路调控间充质干细胞成骨分化的研究进展[J]. 上海交通大学学报：医学版，2013， 33 (1)： 99-103.

[15] 李宝新，李玉坤. Wnt信号通路对骨调节研究新进展[J]. 国际骨科学杂志，2008，45(3)：179-181.

脱氧雪腐镰刀菌烯醇致小鼠畸形骨骼组织差异表达基因及相关通路分析

Differential gene expression and related pathways of skeletal malformations induced by deoxynivalenol in mice

PDF

可视化

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 15

编辑推荐

Metrics

本文评价

[1]	国瑞贤, 谢广云, 韩莹. 基于转录组测序方法研究加替沙星对小鼠的肝损伤作用[J]. 癌变·畸变·突变, 2022, 34(1): 20-24.
[2]	王苗, 王全凯, 李昕苇, 马顺鹏, 乌瀚宝栎尔, 许建宁. 甲基丙烯酸环氧丙酯诱导16HBE细胞恶性转化相关m⁶A修饰异常mRNA的分析[J]. 癌变·畸变·突变, 2021, 33(6): 405-409.
[3]	杨婵君, 陈雯恬, 刘静. 胶原蛋白作为胃癌潜在生物标志物的生物信息学分析[J]. 癌变·畸变·突变, 2021, 33(6): 410-419.
[4]	田薇, 方延, 吴晗恬, 吉布强, 夏昭林. 长链非编码RNA与mRNA在急性髓性白血病中的异常表达及其功能初探[J]. 癌变·畸变·突变, 2021, 33(2): 110-115.
[5]	古丽扎热叶·艾库拉, 谭遥, 帕力达·阿皮孜阿吉. 新疆哈萨克族食管鳞癌与长链非编码RNA表达的关系[J]. 癌变·畸变·突变, 2020, 32(3): 194-197,202.
[6]	王冰玉, 蔡颖, 郑凯, 谢红卫, 徐新云. PM_2.5对HBE细胞致癌致突变相关基因表达的影响[J]. 癌变·畸变·突变, 2020, 32(1): 33-38,42.
[7]	马莉莉, 张树丽, 李琴, 许彭, 封敏, 李秀梅. 新疆哈萨克族食管癌与正常组织间差异表达miRNA的筛查及验证[J]. 癌变·畸变·突变, 2020, 32(1): 52-56.
[8]	曾蕾, 徐雪莲, 罗曼曼, 张凡, 韩志坚, 李玉民. 胃癌基因表达谱芯片差异基因的生物信息学分析[J]. 癌变·畸变·突变, 2019, 31(4): 300-307.
[9]	高杰, 张晓, 魏超. 差异表达miRNA在胰腺癌预后判断中的价值[J]. 癌变·畸变·突变, 2019, 31(3): 173-179.
[10]	董强, 解琪琪, 胡建宏, 王茂林, 袁国强, 潘亚文. 基于生物信息学方法分析甲酰肽受体1在胶质瘤中的表达及临床意义[J]. 癌变·畸变·突变, 2018, 30(6): 457-462.
[11]	李建国,秦秀军,袁慧,张伟,周晋源,闻建华. γ射线诱导大鼠外周血淋巴细胞差异表达基因及相关通路的研究[J]. 癌变·畸变·突变, 2013, 25(6): 435-438.
[12]	王媛媛1/宋光2/李玉梅1/吕洪波1. 与结肠癌转移倾向相关的细胞粘附基因的筛查[J]. 癌变·畸变·突变, 2012, 24(6): 418-421.
[13]	张伟，秦秀军，许超琪，李炜宾，尹晶晶，袁慧，李建国. γ射线照后不同时间点人肝细胞基因差异表达谱的研究[J]. , 2011, 23(6): 416-420.
[14]	刘凤英，靳溪，汤树生，陈倩，张婷，赵文霞，张朝明，张燊，肖希龙*. 喹烯酮诱导HepG2 细胞DNA复制相关基因表达水平的变化[J]. , 2011, 23(5): 325-329.
[15]	石嘉俪(综述), 周佳青*(审校). 甲状腺癌侵袭性相关的分子生物学研究进展[J]. , 2011, 23(4): 319-321.