SEARCH

SEARCH BY CITATION

Keywords:

  • hepatic stellate cells;
  • myofibroblasts;
  • elastin;
  • liver cirrhosis

Abstract:

Background/Aims:

Activated hepatic stellate cells (HSC) are regarded as the principal cells synthesizing extracellular matrix components in fibrotic liver. Elastin content is increased in cirrhotic livers, but the cellular source is not known. Contribution of HSC to the production of elastin was investigated.

Methods:

Expression of elastin in CCl4-cirrhotic rat liver was studied by immunohistochemistry and in situ hybridization, liver myofibroblasts were identified in histological sections by α-smooth muscle actin (α-SMA) staining. LightCycler PCR and Northern blotting were used to detect tropoelastin mRNA in isolated HSC; tropoelastin protein was detected in the cells and in cell-conditioned medium by Western blotting.

Results:

HSC, isolated from normal rat liver, displayed increasing tropoelastin mRNA expression during transdifferentiation in culture. Expression of tropoelastin mRNA was accompanied by the production of tropoelastin protein in vitro. Increased levels of tropoelastin transcripts were found in the connective tissue septa of CCl4-cirrhotic rats and co-localized with α-SMA positive cells. Immunohistochemistry demonstrated elastin presence in the septa.

Conclusion:

HSC express tropoelastin and its expression increases during transdifferentiation to myofibroblast-like cells.