RGD Reference Report - Hypoxia-induced VEGF and collagen I expressions are associated with angiogenesis and fibrogenesis in experimental cirrhosis. - Rat Genome Database

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Hypoxia-induced VEGF and collagen I expressions are associated with angiogenesis and fibrogenesis in experimental cirrhosis.

Authors: Corpechot, C  Barbu, V  Wendum, D  Kinnman, N  Rey, C  Poupon, R  Housset, C  Rosmorduc, O 
Citation: Corpechot C, etal., Hepatology 2002 May;35(5):1010-21.
RGD ID: 634296
Pubmed: PMID:11981751   (View Abstract at PubMed)
DOI: DOI:10.1053/jhep.2002.32524   (Journal Full-text)

Cirrhosis consists of hepatocyte nodules surrounded by a highly vascularized fibrous tissue. We previously showed that the development of biliary cirrhosis in the rat is associated with the occurrence of hepatocellular hypoxia and the induction of hepatic angiogenesis. We herein examined the occurrence of hypoxia in an experimental model of diethylnitrosamine (DEN)-induced cirrhosis. We also determined whether hypoxia directly affects the expression of vascular endothelial growth factor (VEGF), of VEGF receptors (Flt-1, Flk-1), and of type I and type IV collagens in activated hepatic stellate cells (HSCs) and the expression of VEGF in hepatocytes. Our results show that in DEN-treated rats, although the progression of liver fibrosis is associated with hepatocellular hypoxia and angiogenesis, VEGF and Flt-1 expressions in the liver are increased and correlated with the density of microvessels. In vitro, hypoxia induces the expression of VEGF, Flt-1, and type I collagen in activated HSCs and that of VEGF in hepatocytes. In addition, we show that hypoxia-induced type I collagen expression in HSCs may occur independently of transforming growth factor beta1 (TGF-beta1) overexpression. In conclusion, the present study provides further evidence that hepatocellular hypoxia and angiogenesis progress together with fibrogenesis after liver injury and that hypoxia directly contributes to the progression of liver fibrosis.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
liver cirrhosis  ISOFlt1 (Rattus norvegicus)634296; 634296mRNA:increased expressin:liver:RGD 
liver cirrhosis  IEP 634296mRNA:increased expressin:liver:RGD 

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
cellular response to hypoxia  IEP 634296 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Flt1  (Fms related receptor tyrosine kinase 1)

Genes (Mus musculus)
Flt1  (FMS-like tyrosine kinase 1)

Genes (Homo sapiens)
FLT1  (fms related receptor tyrosine kinase 1)

Objects referenced in this article
Gene Vegfa vascular endothelial growth factor A Rattus norvegicus

Additional Information