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

Curr Eye Res. 2025 Jan 16:1-10. doi: 10.1080/02713683.2025.2452919. Online ahead of print.

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.

Keywords: DNA motif; MMP; Pterygium; cohesin; transcription.