Scholarlink

Background and methods <p>Hypoxia, glycolysis, and lactylation are key processes in liver fibrosis (LF) and hepatocarcinogenesis, yet the role of hypoxia-, glycolysis-, and lactylation-related genes (HGLRGs) in LF is poorly defined. Here, we systematically analyzed transcriptomic data from LF samples to identify differentially expressed HGLRGs, validate by single-cell transcriptomics, construct co-expression networks, evaluate their biological functions, diagnostic performance, immune relevance, and explore potential therapeutic agents.</p> Results <p>Seven HGLRGs—CHST4, FABP5, GPC3, SOX9, SRPX, IFI16, and ISG20—were significantly upregulated in LF and demonstrated strong diagnostic value. FABP5 and ISG20 were consistently elevated in activated stellate cells and human cirrhotic livers. Enrichment analyses indicated that these genes modulate metabolic pathways and drive immune-mediated fibrotic responses. Immune profiling revealed that ISG20 expression inversely correlated with resting NK cell infiltration, and SOX9 with M2 macrophage infiltration. Molecular docking identified seven FDA-approved drugs, including aspirin, Methylene blue, tamoxifen, vorinostat, valproic acid, rosiglitazone and acetaminophen, as potential HGLRG-targeting agents.</p> Conclusion <p>HGLRGs are aberrantly upregulated and actively contribute to LF progression through metabolic dysregulation and immune remodeling. FABP5 and ISG20 represents promising biomarkers and therapeutic target. This study providing novel diagnostic markers, drug repurposing opportunities, and strategies for improved clinical management of liver cirrhosis.</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

The impact of hypoxia and glycolysis on liver fibrosis

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年5月16日

查看全文
  • Yun Li,
  • Fusheng Qin,
  • Hanyang Su,
  • Jianguo Li

摘要

Background and methods

Hypoxia, glycolysis, and lactylation are key processes in liver fibrosis (LF) and hepatocarcinogenesis, yet the role of hypoxia-, glycolysis-, and lactylation-related genes (HGLRGs) in LF is poorly defined. Here, we systematically analyzed transcriptomic data from LF samples to identify differentially expressed HGLRGs, validate by single-cell transcriptomics, construct co-expression networks, evaluate their biological functions, diagnostic performance, immune relevance, and explore potential therapeutic agents.

Results

Seven HGLRGs—CHST4, FABP5, GPC3, SOX9, SRPX, IFI16, and ISG20—were significantly upregulated in LF and demonstrated strong diagnostic value. FABP5 and ISG20 were consistently elevated in activated stellate cells and human cirrhotic livers. Enrichment analyses indicated that these genes modulate metabolic pathways and drive immune-mediated fibrotic responses. Immune profiling revealed that ISG20 expression inversely correlated with resting NK cell infiltration, and SOX9 with M2 macrophage infiltration. Molecular docking identified seven FDA-approved drugs, including aspirin, Methylene blue, tamoxifen, vorinostat, valproic acid, rosiglitazone and acetaminophen, as potential HGLRG-targeting agents.

Conclusion

HGLRGs are aberrantly upregulated and actively contribute to LF progression through metabolic dysregulation and immune remodeling. FABP5 and ISG20 represents promising biomarkers and therapeutic target. This study providing novel diagnostic markers, drug repurposing opportunities, and strategies for improved clinical management of liver cirrhosis.