RGD Reference Report - Regulatory role of vHL/HIF-1alpha in hypoxia-induced VEGF production in hepatic stellate cells. - Rat Genome Database

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Regulatory role of vHL/HIF-1alpha in hypoxia-induced VEGF production in hepatic stellate cells.

Authors: Wang, YQ  Luk, JM  Ikeda, K  Man, K  Chu, AC  Kaneda, K  Fan, ST 
Citation: Wang YQ, etal., Biochem Biophys Res Commun. 2004 Apr 30;317(2):358-62.
RGD ID: 1580561
Pubmed: PMID:15063765   (View Abstract at PubMed)
DOI: DOI:10.1016/j.bbrc.2004.03.050   (Journal Full-text)

Activated hepatic stellate cells (HSCs) produce cyclooxygenase-2 (COX-2) protein to induce vascular endothelial growth factor (VEGF) production that participates in angiogenesis in injured liver. To reveal the unknown regulatory mechanism, we used hypoxic atmosphere mimicking injured-tissue microenvironment to induce VEGF expression in a rat hepatic stellate cell line (T6-HSCs). The present study showed that hypoxia up-regulated the protein levels of COX-2 and hypoxia-inducible factor-1-alpha (HIF-1alpha), but rapidly effected degradation of von Hippel-Lindau (vHL) protein. As a result, expression of VEGF in HSCs was markedly elevated; and pretreatment with COX-2 inhibitors (nimesulide or indomethacin) could significantly ameliorate the angiogenic event. Collectively, hypoxic HSCs increased accumulation of HIF-1alpha protein and induced VEGF expression in a time-dependent manner. Inhibition of COX-2 activities would prevent vHL protein from degradation and suppress HIF-1alpha up-regulation. Thus, vHL/HIF-1alpha has a regulatory role in COX-2-mediated VEGF production in hypoxic stellate cells in injured liver.

Molecular Pathway Annotations    Click to see Annotation Detail View

RGD Manual Annotations

Objects Annotated

Genes (Rattus norvegicus)
Hif1a  (hypoxia inducible factor 1 subunit alpha)
Vhl  (von Hippel-Lindau tumor suppressor)

Genes (Mus musculus)
Hif1a  (hypoxia inducible factor 1, alpha subunit)
Vhl  (von Hippel-Lindau tumor suppressor)

Genes (Homo sapiens)
HIF1A  (hypoxia inducible factor 1 subunit alpha)
VHL  (von Hippel-Lindau tumor suppressor)

Objects referenced in this article
Gene VEGFA vascular endothelial growth factor A Homo sapiens
Gene Vegfa vascular endothelial growth factor A Mus musculus
Gene Vegfa vascular endothelial growth factor A Rattus norvegicus

Additional Information