TargetRx Atlas

MRNA basic information

  • mRNA ID:ENST00000374391
  • Gene Name:ALOX5
  • mRNA database:Ensembl
  • mRNA expression :down-regulated
  • mRNA Method:PCR
  • mRNA Pathway:NA
  • Evidence:validated
  • (mRNA-drug)

Drug basic information

  • Drug ID:DB00744
  • Drug Name:Zileuton
  • Drug Method:down-regulated the gene expression

Disease basic infommation

  • Disease:hepatic fibrosis
  • Tissue:tissues

Other information

  • Title:Inhibition of 5-Lipoxygenase in Hepatic Stellate Cells Alleviates Liver Fibrosis
  • Journal:Frontiers in Pharmacology
  • Published:2021
  • PubMed ID:33679410
  • Abstract:Background and Purpose:Activation of hepatic stellate cells (HSC) is a central driver of liver fibrosis. 5-lipoxygenase (5-LO) is the key enzyme that catalyzes arachidonic acid into leukotrienes. In this study, we examined the role of 5-LO in HSC activation and liver fibrosis.Main Methods:Culture medium was collected from quiescent and activated HSC for target metabolomics analysis. Exogenous leukotrienes were added to culture medium to explore their effect in activating HSC. Genetic ablation of 5-LO in mice was used to study its role in liver fibrosis induced by CCl4and a methionine-choline-deficient (MCD) diet. Pharmacological inhibition of 5-LO in HSC was used to explore the effect of this enzyme in HSC activation and liver fibrosis.Key Results:The secretion of LTB4and LTC4was increased in activated vs. quiescent HSC. LTB4and LTC4contributed to HSC activation by activating the extracellular signal-regulated protein kinase pathway. The expression of 5-LO was increased in activated HSC and fibrotic livers of mice. Ablation of 5-LO in primary HSC inhibited both mRNA and protein expression of fibrotic genes. In vivo, ablation of 5-LO markedly ameliorated the CCl4- and MCD diet-induced liver fibrosis and liver injury. Pharmacological inhibition of 5-LO in HSC by targeted delivery of the 5-LO inhibitor zileuton suppressed HSC activation and improved CCl4- and MCD diet-induced hepatic fibrosis and liver injury. Finally, we found increased 5-LO expression in patients with non-alcoholic steatohepatitis and liver fibrosis.Conclusion:5-LO may play a critical role in activating HSC; genetic ablation or pharmacological inhibition of 5-LO improved CCl4-and MCD diet-induced liver fibrosis.
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