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公共数据挖掘结合国内实验研究确定了尚未明确特征的老年基因基质重塑相关7(MXRA7)在眼部生理病理学中的作用。

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.

作者信息

Jia Changkai, Zhang Feng, Zhu Ying, Qi Xia, Wang Yiqiang

机构信息

Shandong Provincial Key Lab of Ophthalmology, Shandong Eye Institute, Shandong Academy of Medical Sciences, Qingdao, China.

Eye Clinic, Linyi People's Hospital, Linyi, China.

出版信息

Gene. 2017 Oct 20;632:43-49. doi: 10.1016/j.gene.2017.08.018. Epub 2017 Aug 26.

DOI:10.1016/j.gene.2017.08.018
PMID:28847716
Abstract

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.

摘要

基质重塑相关7(MXRA7)基因于2002年首次被报道,因其与几个已知与基质重塑相关的基因共表达而得名。然而,尚未有任何研究特意对该基因进行特征描述。我们通过整合生物信息学分析和实验研究来开始确定MXRA7的功能。在BioGPS、基因表达综合数据库(Gene Expression Omnibus)和EurExpress平台上对MXRA7表达进行数据挖掘,结果突出显示了Mxra7在小鼠眼部组织中的高水平表达。采用实时定量聚合酶链反应(Real-time PCR)来检测成年C57BL/6小鼠组织中的Mxra7信使核糖核酸(mRNA),结果表明Mxra7在视网膜、角膜和晶状体中的表达水平优先高于其他组织。随后在Balb/c小鼠中诱导炎性角膜新生血管化(CorNV)模型和真菌性角膜感染,并通过逆转录聚合酶链反应(RT-PCR)监测Mxra7以及几个与基质重塑相关基因(基质金属蛋白酶3(Mmp3)、基质金属蛋白酶13(Mmp13)、细胞外基质蛋白1(Ecm1)、基质金属蛋白酶组织抑制剂1(Timp1))的mRNA水平。结果显示出一种随时间变化的Mxra7低表达模式(沿时间线呈U形曲线),而所有其他与基质重塑相关的基因则呈现相反的变化模式(穹顶形曲线)。当查看BioGPS中关于人类MXRA7基因在人体组织中表达的有限数据时,发现眼部组织也是MXRA7表达水平最高的组织。总之,在公共数据库以及家畜模型中对MXRA7基因表达进行的综合分析表明,MXRA7在小鼠和人类眼部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表明,MXRA7可能在涉及损伤、新生血管化和伤口愈合的病理过程或疾病中发挥作用。

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