TargetRx Atlas

MRNA basic information

  • mRNA ID:ENST00000672860
  • Gene Name:VEGFA
  • mRNA database:Ensembl
  • mRNA expression :down-regulated
  • mRNA Method:qRT-PCR
  • mRNA Pathway:NA
  • Evidence:validated
  • (mRNA-drug)

Drug basic information

  • Drug ID:DB06589
  • Drug Name:Pazopanib
  • Drug Method:down-regulated the gene expression

Disease basic infommation

  • Disease:hepatic fibrosis
  • Tissue:patients tissues

Other information

  • Title:The multi-kinase inhibitor pazopanib targets hepatic stellate cell activation and apoptosis alleviating progression of liver fibrosis
  • Journal:Naunyn-schmiedebergs Archives of Pharmacology
  • Published:2015
  • PubMed ID:26269412
  • Abstract:Tyrosine kinase inhibitors have been emerged recently as an effective therapy against liver fibrosis. The current study was designed to test a potential anti-fibrotic effect of the multi-targeted receptor tyrosine kinase inhibitor pazopanib. Carbon tetrachloride (CCl4; 1 mL/kg) was injected intraperitoneally (i.p.) twice/week for 8 weeks. Pazopanib (10 and 30 mg/kg, i.p.) was administered three times/week at the beginning of week 5. Levels of liver function biomarkers (alanine aminotransferase (ALT), aspartate aminotransferase (AST), albumin, and total bilirubin), malondialdehyde, transforming growth factor-β1 (TGF-β1), caspase-3, factor-related apoptosis (FAS), vascular endothelial growth factor (VEGF) receptor-1, and pigment endothelial derived factor (PEDF) were measured. The tissue level of the inflammatory cytokines IL-6 and tumor necrosis factor-α (TNF-α) were assigned. Fibrotic area was measured by morphometry and expression of alpha-smooth muscle actin (α-SMA), caspase-3, platelet-derived growth factor (PDGF) receptor-β, and matrix metalloproteinase-2 (MMP-2) was scored immunohistochemically. Hepatic expression of collagen-1-alpha-1 (Col1A1) and tissue inhibitor metalloproteinase-1 (TIMP-1) mRNA were assigned by RT-qPCR. Injection of CCl4 resulted in marked collagen deposition, necroinflammation, and fibrosis (2.67%). Pazopanib in a dose of 30 mg/kg improved liver function, reduced fibrosis (1.48%), and decreased significantly (P < 0.01) liver expression of malondialdehyde, TGF-β1, IL-6, TNF-α, Col1A1, TIMP-1, α-SMA, MMP-2, PDGF receptor-β, and VEGF receptor-1. Additionally, the apoptotic markers (caspase-3, FAS) and the anti-angiogenic factor PEDF were upregulated significantly (P < 0.05). Pazopanib at a certain dose level can halt liver fibrosis progression through modulating inflammatory cytokines, suppressing stellate cell activity, inducing apoptosis, and potentially regulating angiogenesis.
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