
浏览全部资源
扫码关注微信
400038 重庆,陆军军医大学(第三军医大学)军事预防医学系军队劳动卫生学教研室,电磁辐射医学防护教育部重点实验室
[余争平,E-mail:yuzping_tmmu@126.com YU Zhengping, E-mail: yuzping_tmmu@126.com
收稿:2020-08-18,
修回:2020-09-28,
纸质出版:2020-12-15
移动端阅览
卢永辉, 陈纯海, 高鹏, 等. 太赫兹辐射暴露引起小鼠视网膜基因表达改变[J]. 第三军医大学学报, 2020,43(23):2274-2281.
Yonghui LU, Chunhai CHEN, Peng GAO, et al. Terahertz radiation exposure results in altered gene expression profile in mouse retina[J]. Journal of Third Military Medical University, 2020, 43(23): 2274-2281.
卢永辉, 陈纯海, 高鹏, 等. 太赫兹辐射暴露引起小鼠视网膜基因表达改变[J]. 第三军医大学学报, 2020,43(23):2274-2281. DOI: 10.16016/j.1000-5404.202008140.
Yonghui LU, Chunhai CHEN, Peng GAO, et al. Terahertz radiation exposure results in altered gene expression profile in mouse retina[J]. Journal of Third Military Medical University, 2020, 43(23): 2274-2281. DOI: 10.16016/j.1000-5404.202008140.
目的
2
探讨太赫兹(terahertz,THz)辐射暴露后视网膜组织基因表达变化的整体情况,揭示THz暴露所致视觉系统损伤效应的关键信号通路及关键基因。
方法
2
通过
平均功率密度80 mW/cm
2
的THz辐射暴露小鼠眼部,暴露时长2 min,取暴露后视网膜组织,采用RNA-seq测序分析基因表达变化的整体差异,采用聚类分析及富集分析揭示差异基因富集的信号通路和所揭示的生物功能;并进一步通过Real-time PCR揭示THz辐射暴露对视网膜损伤关键基因表达影响的时效关系。
结果
2
以
P
<
0.05、|logFC|≥1为筛选条件对差异表达基因进行筛选,共筛选出上调基因625个,下调基因9个。GO分析差异基因主要分布于细胞外成分,分子功能主要为影响蛋白结合等,生物功能主要为细胞应激反应与细胞增殖等。KEGG信号通路分析结果显示,差异基因主要影响PPAR信号通路、癌症相关信号通路、钙离子信号通路及PI3K-Akt信号通路。通过Real-time PCR对视网膜损伤相关基因进行验证发现,在暴露后5 min及24 h,THz辐射暴露均上调
Krt12
、
Cfd
、
Wnt3a
及
Adipoq
表达,下调
Foxe3
、
Serpine3
、
Lix1
、
Rpe65
、
Rgr
及
Arsi
基因表达,且暴露后5 min上调或下调幅度明显强于24 h。
结论
2
THz辐射能够导致视网膜大量基因表达异常,提示THz暴露可能造成视网膜损伤。
Objective
2
To explore the global changes of gene expression profile in the retina after terahertz (THz) radiation exposure in order to reveal the signal pathways and key genes involved in the process of visual system damage.
Methods
2
Mouse eyes were exposed to THz radiation at an average power density of 80 mW for 2 min. Then the retinal tissues were harvested to extract total RNA for RNA-seq analysis. The differential expression genes (DEGs) and their functions were identified with a certain condition for Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Real-time PCR was used to further explore the time-dependent effects of THz exposure on the expression of the key genes related to retinal injury from DEGs.
Results
2
There were 625 up-regulated genes and 9 down-regulated genes screened out through the condition of
P
<
0.05 and |logFC|≥1. The GO analysis revealed that the DEGs were mainly composed of extracellular components as the complementary biological concept of cellular component (CC)
mainly related to protein
binding as the concept of molecular function (MF)
and were associated with response to external stimulus and cell proliferation as the concept of biological process (BP). The KEGG analysis indicated that most DEGs were enriched in the PPAR
PI3K-Akt
and tumor- and calcium-related signaling pathways. Real-time PCR displayed that the expression levels of Krt12
Cfd
Wnt3a and Adipoq were up-regulated
while those of
Krt12
Cfd
Wnt3a
and
Adipoq
were up-regulated
while those of
Foxe3
Serpine3
Lix1
Rpe65
Rgr
and
Arsi
were down-regulated in the injured retinal tissues after THz irradiation exposure for 5 min and 24 h
and the changes were more significant after 5 minutes' than 24 hours' exposure.
Conclusion
2
THz radiation exposure causes abnormal expression of a large number of genes in retinal tissue
indicating the exposure may induce retinal injury.
WANG C L, GONG J X, XING Q R, et al . Application of terahertz time-domain spectroscopy in intracellular metabolite detection[J ] . J Biophotonics, 2010, 3(10/11): 641-645. DOI:10.1002/jbio.201000043.
CHEON H, YANG H J, LEE S H, et al . Terahertz molecular resonance of cancer DNA[J ] . Sci Rep, 2016, 6: 37103. DOI:10.1038/srep37103.
LIU Y, ZHOU T, CAO J C. Terahertz spectral of enantiomers and racemic amino acids by time-domain-spectroscopy technology[J]. Infrared Phys Technol, 2019, 96: 17-21. DOI:10.1016/j.infrared.2018.10.026.
HAN X, YAN S, ZANG Z, et al . Label-free protein detection using terahertz time-domain spectroscopy[J ] . Biomed Opt Express, 2018, 9(3): 994-1005. DOI:10.1364/boe.9.000994.
LI T, MA H, PENG Y, et al . Gaussian numerical analysis and terahertz spectroscopic measurement of homocysteine[J ] . Biomed Opt Express, 2018, 9(11): 5467-5476. DOI:10.1364/boe.9.005467.
CHEN W, PENG Y, JIANG X, et al . Isomers identification of 2-hydroxyglutarate acid disodium salt (2HG) by terahertz time-domain spectroscopy[J ] . Sci Rep, 2017, 7(1): 12166. DOI:10.1038/s41598-017-11527-z.
RONG L, LATYCHEVSKAIA T, CHEN C, et al . Terahertz in-line digital holography of human hepatocellular carcinoma tissue[J ] . Sci Rep, 2015, 5: 8445. DOI:10.1038/srep08445.
FAN S, UNG B S Y, PARROTT E P J, et al . In vivo terahertz reflection imaging of human scars during and after the healing process[J ] . J Biophotonics, 2017, 10(9): 1143-1151. DOI:10.1002/jbio.201600171..
HWANG Y, AHN J, MUN J, et al . In vivo analysis of THz wave irradiation induced acute inflammatory response in skin by laser-scanning confocal microscopy[J ] . Opt Express, 2014, 22(10): 11465-11475. DOI:10.1364/oe.22.011465..
WILMINK G J, RIVEST B D, ROTH C C, et al . In vitro investigation of the biological effects asso ciated with human dermal fibroblasts exposed to 2.52 THz radiation[J ] . Lasers Surg Med, 2011, 43(2): 152-163. DOI:10.1002/lsm.20960..
PERERA P, APPADOO D, CHEESEMAN S, et al . PC 12 pheochromocytoma cell response to super high frequency terahertz radiation from synchrotron source[J ] . Cancers, 2019, 11(2): 162. DOI:10.3390/cancers11020162.
WESTHEIMER G. Focused and defocused retinal images with Bessel and axicon pupil functions[J]. J Opt Soc Am A, 2020, 37(1): 108. DOI:10.1364/josaa.37.000108.
WILMINK G J, GRUNDT J E. Invited review article: current state of research on biological effects of terahertz radiation[J]. J Infrared Millim Terahertz Waves, 2011, 32(10): 1074-1122. DOI:10.1007/s10762-011-9794-5.
ZHANG H, GONG M, LUO X L. Methoxytetrahydro-2H-pyran-2-yl)methyl benzoate inhibits spinal cord injury in the rat model via PPAR-γ/PI3K/p-Akt activation[J ] . Environ Toxicol, 2020, 35(6): 714-721. DOI:10.1002/tox.22902.
BOUSSADIA B, GANGAROSSA G, MSELLI-LAKHAL L, et al . Lack of CAR impacts neuronal function and cerebrovascular integrity in vivo [J ] . Exp Neurol, 2016, 283(part A): 39-48. DOI:10.1016/j.expneurol.2016.05.018..
ZENKE F T, ZIMMERMANN A, SIRRENBERG C, et al . Pharmacologic inhibitor of DNA-PK, M3814, potentiates radiotherapy and regresses human tumors in mouse models[J ] . Mol Cancer Ther, 2020, 19(5): 1091-1101. DOI:10.1158/1535-7163.mct-19-0734.
YANG U, GENTLEMAN S, GAI X, et al . Utility of in vitro mutagenesis of RPE65 protein for verification of mutational pathogenicity before gene therapy[J ] .JAMA Ophthalmol, 2019, 137(12):1-9. DOI: 10.1001/jamaophthalmol. 2019.3914..
LI S, XIAO X, YI Z, et al . RPE65 mutation frequency and phenotypic variation according to exome sequencing in a tertiary centre for genetic eye diseases in China[J ] . Acta Ophthalmol, 2020, 98(2): e181-e190. DOI:10.1111/aos.14181.
MORSHEDIAN A, KAYLOR J J, NG S Y, et al . Light-driven regeneration of cone visual pigments through a mechanism involving RGR opsin in Müller glial cells[J ] . Neuron, 2019, 102(6): 1172-1183.e5. DOI:10.1016/j.neuron.2019.04.004.
OSHIKAWA M, USAMI R, KATO S. Characterization of the arylsulfatase I (ARSI) gene preferentially expressed in the human retinal pigment epithelium cell line ARPE-19[J]. Mol Vis, 2009, 15:482-494.
LI H Y, HONG X, CAO Q Q, et al .Adiponectin, exercise and eye diseases[J ] . Int Rev Neurobiol, 2019, 147:281-294.DOI: 10.1016/bs.irn.2019.07.006.
TRZECIECKA A, CARMY T, HACKAM A S, et al . Lipid profiling dataset of the Wnt3a-induced optic nerve regeneration[J ] . Data Brief, 2019, 25: 103966. DOI:10.1016/j.dib.2019.103966.
MCKEY J, MARTIRE D, DE SANTA BARBARA P, et al . LIX1 regulates YAP1 activity and controls the proliferation and differentiation of stomach mesenchymal progenitors[J ] . BMC Biol, 2016, 14:34.DOI: 10.1186/s12915-016-0257-2.
NISHINO T, KOBAYASHI A, MORI N, et al . In vivo histology and p.L132V mutation in KRT12 gene in Japanese patients with Meesmann corneal dystrophy[J ] . Jpn J Ophthalmol, 2019, 63(1): 46-55. DOI:10.1007/s10384-018-00643-6..
LIN R, FU X, LEI C, et al . Intravitreal injection of amyloid β1-42 activates the complement system and induces retinal inflammatory responses and malfunction in mouse[J ] . Adv Exp Med Biol, 2019, 1185: 347-352. DOI:10.1007/978-3-030-27378-1_57.
ROHRER B, GUO Y, KUNCHITHAPAUTHAM K, et al . Eliminating complement factor D reduces photoreceptor susceptibility to light-induced damage[J ] . Invest Ophthalmol Vis Sci, 2007, 48(11): 5282-5289. DOI:10.1167/iovs.07-0282.
WILLIAMS J A, STAMPOULIS D, GUNTER C E, et al . Regulation of C3 activation by the alternative complement pathway in the mouse Retina[J ] . PLoS ONE, 2016, 11(8): e0161898. DOI:10.1371/journal.pone.0161898.
0
浏览量
0
下载量
0
CSCD
关联资源
相关文章
相关作者
相关机构
京公网安备11010802024621