Altered Expression Levels of MMP1, MMP9, MMP12, TIMP1, and IL-1β as a Risk Factor for the Elevated IOP and Optic Nerve Head Damage in the Primary Open-Angle Glaucoma Patients.

Altered Expression Levels of MMP1, MMP9, MMP12, TIMP1, and IL-1β as a Risk Factor for the Elevated IOP and Optic Nerve Head Damage in the Primary Open-Angle Glaucoma Patients.
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DOI:
10.1155/2015/812503
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发表时间:
2015
影响因子:
--
通讯作者:
Majsterek I
Majsterek I
中科院分区:
生物学3区
文献类型:
--
作者:
Markiewicz L;Pytel D;Mucha B;Szymanek K;Szaflik J;Szaflik JP;Majsterek I

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本研究的目的是分析POAG患者-1607 1G/2G MMP 1、-1562 C/T MMP 9、-82 A/G MMP 12、-511 C/T IL-1β和372 T/C TIMP 1基因启动子区的特定多态性变化对其表达水平的影响。从50名POAG患者和50名对照受试者获得的血液和房水样品用于QPCR和通过ELISA的蛋白质水平分析。使用双荧光素酶测定对HTM细胞进行体内启动子活性测定。所有研究受试者均接受眼科检查,包括BCVA、眼内压、裂隙灯检查、前房角镜检查、HRT和OCT扫描。POAG患者MMP 1、MMP 9、MMP 12和IL-1β基因mRNA表达较对照组明显增高(P < 0.001)。POAG患者眼房水中MMP 1、MMP 9、MMP 12和IL-1β的蛋白表达均高于对照组(P < 0.001)。MMP 1基因的-1607 1G等位基因仅具有-1607 2G等位基因转录活性的42.91%,MMP 9基因的-1562 C等位基因仅具有-1562 T等位基因转录活性的21.86%。金属蛋白酶表达水平的增加可以被认为是POAG发展的危险因素。
The aim of presented work was to analyze the impact of particular polymorphic changes in the promoter regions of the -1607 1G/2G MMP1, -1562 C/T MMP9, -82 A/G MMP12, -511 C/T IL-1β, and 372 T/C TIMP1 genes on their expression level in POAG patients. Blood and aqueous humor samples acquired from 50 patients with POAG and 50 control subjects were used for QPCR and protein levels analysis by ELISA. In vivo promoter activity assays were carried on HTM cells using dual luciferase assay. All studied subjects underwent ophthalmic examination, including BCVA, intraocular pressure, slit-lamp examination, gonioscopy, HRT, and OCT scans. Patients with POAG are characterized by an increased mRNA expression of MMP1, MMP9, MMP12, and IL-1β genes as compared to the control group (P < 0.001). Aqueous humor acquired from patients with POAG displayed increased protein expression of MMP1, MMP9, MMP12, and IL-1β compared to the control group (P < 0.001). Allele -1607 1G of MMP1 gene possesses only 42,91% of the -1607 2G allele transcriptional activity and allele -1562 C of MMP9 gene possesses only 21,86% of the -1562 T allele. Increased expression levels of metalloproteinases can be considered as a risk factor for the development of POAG.
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