Scholarlink

<p>Pterygium, a common ocular surface disorder, is associated with environmental factors such as ultraviolet exposure and air pollution. Tris(1,3-dichloro-2-propyl) phosphate (TDCPP), a widely used organophosphate flame retardant, has been detected in environmental and biological samples, yet its role in pterygium pathogenesis remains unclear. This study employed an integrative approach combining network toxicology, transcriptome sequencing, and in vitro cytotoxicity assays to elucidate the molecular mechanisms linking TDCPP exposure to pterygium development. Bioinformatics analysis identified 273 TDCPP-related targets and 1,078 pterygium-associated genes, with 43 overlapping candidates. Weighted gene co-expression network analysis (WGCNA) revealed two key modules correlated with pterygium phenotypes, highlighting <i>MMP3</i> as a central regulator. Molecular docking and dynamics simulations confirmed stable interactions between TDCPP and <i>MMP3</i> (binding energy: -5.9&#xa0;kcal/mol), supported by RMSD, RMSF, and hydrogen bonding analyses. In vitro experiments demonstrated that low-dose TDCPP (0.5 µM) upregulated <i>MMP3</i> expression in immortalized human conjunctival fibroblasts, enhancing cell proliferation, while higher concentrations (50 µM) induced cytotoxicity. These findings suggest that TDCPP promotes pterygium pathogenesis via MMP3-mediated extracellular matrix remodeling and fibroblast proliferation. This study provides novel insights into the environmental etiology of pterygium and identifies <i>MMP3</i> as a potential therapeutic target for TDCPP-associated ocular surface disorders.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Network toxicology, transcriptomics, and cytotoxic validation reveal TDCPP-induced pterygium mechanisms

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年11月7日

查看全文
  • Ji Yang,
  • Jiajie Li,
  • Boyu Liang,
  • Nishan Zhao,
  • Peng Zhang,
  • ChengYan Fang,
  • Tao Xie,
  • Ping Xiang,
  • Hai Liu

摘要

Pterygium, a common ocular surface disorder, is associated with environmental factors such as ultraviolet exposure and air pollution. Tris(1,3-dichloro-2-propyl) phosphate (TDCPP), a widely used organophosphate flame retardant, has been detected in environmental and biological samples, yet its role in pterygium pathogenesis remains unclear. This study employed an integrative approach combining network toxicology, transcriptome sequencing, and in vitro cytotoxicity assays to elucidate the molecular mechanisms linking TDCPP exposure to pterygium development. Bioinformatics analysis identified 273 TDCPP-related targets and 1,078 pterygium-associated genes, with 43 overlapping candidates. Weighted gene co-expression network analysis (WGCNA) revealed two key modules correlated with pterygium phenotypes, highlighting MMP3 as a central regulator. Molecular docking and dynamics simulations confirmed stable interactions between TDCPP and MMP3 (binding energy: -5.9 kcal/mol), supported by RMSD, RMSF, and hydrogen bonding analyses. In vitro experiments demonstrated that low-dose TDCPP (0.5 µM) upregulated MMP3 expression in immortalized human conjunctival fibroblasts, enhancing cell proliferation, while higher concentrations (50 µM) induced cytotoxicity. These findings suggest that TDCPP promotes pterygium pathogenesis via MMP3-mediated extracellular matrix remodeling and fibroblast proliferation. This study provides novel insights into the environmental etiology of pterygium and identifies MMP3 as a potential therapeutic target for TDCPP-associated ocular surface disorders.