Public data mining plus domestic experimental study defined involvement of the old-yet-uncharacterized gene matrix-remodeling associated 7 (MXRA7) in physiopathology of the eye

Public data mining plus domestic experimental study defined involvement of the old-yet-uncharacterized gene matrix-remodeling associated 7 (MXRA7) in physiopathology of the eye
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DOI:
10.1016/j.gene.2017.08.018
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发表时间:
2017-10-20
期刊:
影响因子:
3.5
通讯作者:
Wang, Yiqiang
Wang, Yiqiang
中科院分区:
生物学3区
文献类型:
--
作者:
Jia, Changkai;Zhang, Feng;Wang, Yiqiang

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基质重塑相关基因7(MXRA7)是2002年首次报道的一个基因,因其与多个已知的基质重塑相关基因共表达而得名。然而,没有任何研究被有意进行,以表征该基因。我们通过生物信息学分析和实验研究相结合的方法对MXRA7的功能进行了界定。BioGPS、Gene Expression Omnibus和EurExpress平台中MXRA7表达的数据挖掘突出了Mxra7在鼠眼组织中的高水平表达。实时荧光定量PCR检测成年C57 BL/6小鼠视网膜、角膜和透镜中Mxra7 mRNA的表达。建立炎症性角膜新生血管(CorNV)模型和真菌性角膜感染模型,RT-PCR检测Mxra7和基质重塑相关基因(Mmp3、Mmp13、Ecm1、Timp1)的mRNA水平。结果显示,Mxra7呈时间依赖性低表达模式(沿时间轴沿着U形曲线),而所有其他基质重塑相关基因均表现出相反的变化模式(圆顶形曲线)。当查看来自BioGPS的关于人组织中人MXRA7基因表达的有限数据时,发现眼组织也是表达最高水平的MXRA7的组织。总之,在公共数据库以及家养动物模型中的MXRA7基因表达的综合测定显示MXRA7在小鼠和人眼组织中选择性高表达,并且其在两种角膜疾病模型中的变化模式暗示MXRA7可能在涉及损伤、新生血管和伤口愈合的病理过程或疾病中起作用。
Matrix-remodeling associated 7 (MXRA7) gene was first reported in 2002 and named so for its co-expression with several genes known to relate with matrix-remodeling. However, not any studies had been intentionally performed to characterize this gene. We started defining the functions of MXRA7 by integrating bioinformatics analysis and experimental study. Data mining of MXRA7 expression in BioGPS, Gene Expression Omnibus and EurExpress platforms highlighted high level expression of Mxra7 in murine ocular tissues. Real-time PCR was employed to measure Mxra7 mRNA in tissues of adult C57BL/6 mice and demonstrated that Mxra7 was preferentially expressed at higher level in retina, corneas and lens than in other tissues. Then the inflammatory corneal neovascularization (CorNV) model and fungal corneal infections were induced in Balb/c mice, and mRNA levels of Mxra7 as well as several matrix-remodeling related genes (Mmp3, Mmp13, Ecm1 , Timp1) were monitored with RT-PCR. The results demonstrated a time-dependent Mxra7 under-expression pattern (U-shape curve along timeline), while all other matrix-remodeling related genes manifested an opposite changes pattern (dome-shape curve). When limited data from BioGPS concerning human MXRA7 gene expression in human tissues were looked at, it was found that ocular tissue was also the one expressing highest level of MXRA7. To conclude, integrative assay of MXRA7 gene expression in public databank as well as domestic animal models revealed a selective high expression MXRA7 in murine and human ocular tissues, and its change patterns in two corneal disease models implied that MXRA7 might, play a role in pathological processes or diseases involving injury, neovascularization and would healing.