Cohesin Complex Interacting with Promoters of MMP Genes for in Pterygium Occurrence.

IF 1.7 4区 医学 Q3 OPHTHALMOLOGY Current Eye Research Pub Date : 2025-01-16 DOI:10.1080/02713683.2025.2452919
Shichao Han, Wei Zhu, Qianqian Guo
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Abstract

Purpose: Pterygium is a common ocular surface disease characterized by a high recurrence rate and unknown etiology.

Methods: In this study, we investigated the upregulation of matrix metalloproteinase genes, including MMP1, MMP2, MMP3, MMP7, MMP9, MMP11, MMP12, MMP13, MMP23B, and MMP28, in pterygium tissue using RNA sequencing, Western blotting, and immunohistochemistry.

Results: Employing the MEME tool, we identified a conserved DNA motif within the promoter regions of these matrix metalloproteinase genes. Mass spectrometry analysis revealed an interaction between the cohesin complex and this motif. Disrupting the cohesin complex through RNA interference of RAD21 cohesin complex component or structural maintenance of chromosomes 3 in primary pterygial fibroblasts led to decreased matrix metalloproteinase gene expression and reduced recruitment of twist family bHLH transcription factor 1 and transcription factor 4 to matrix metalloproteinase gene promoters.

Conclusion: Overall, our findings suggest a novel epigenetic mechanism regulating matrix metalloproteinase transcription in pterygium.

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内聚蛋白复合物与MMP基因启动子相互作用在翼状胬肉发生中的作用。
目的:翼状胬肉是一种常见的眼表疾病,复发率高,病因不明。方法:本研究采用RNA测序、Western blotting和免疫组化等方法,研究了基质金属蛋白酶基因MMP1、MMP2、MMP3、MMP7、MMP9、MMP11、MMP12、MMP13、MMP23B和MMP28在翼状胬肉组织中的表达上调。结果:利用MEME工具,我们在这些基质金属蛋白酶基因的启动子区域内鉴定了一个保守的DNA基序。质谱分析揭示了内聚复合物和该基序之间的相互作用。通过RNA干扰原代翼状胬肉成纤维细胞RAD21内聚蛋白复合物组分或维持3号染色体结构破坏内聚蛋白复合物,导致基质金属蛋白酶基因表达降低,twist家族bHLH转录因子1和转录因子4募集基质金属蛋白酶基因启动子减少。结论:本研究提示翼状胬肉中存在一种调控基质金属蛋白酶转录的新表观遗传机制。
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来源期刊
Current Eye Research
Current Eye Research 医学-眼科学
CiteScore
4.60
自引率
0.00%
发文量
163
审稿时长
12 months
期刊介绍: The principal aim of Current Eye Research is to provide rapid publication of full papers, short communications and mini-reviews, all high quality. Current Eye Research publishes articles encompassing all the areas of eye research. Subject areas include the following: clinical research, anatomy, physiology, biophysics, biochemistry, pharmacology, developmental biology, microbiology and immunology.
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