Mt. Levy et al., Oncostatin M: a cytokine upregulated in human cirrhosis, increases collagen production by human hepatic stellate cells, J HEPATOL, 32(2), 2000, pp. 218-226
Background/Aims: Hepatic stellate cells are predominantly responsible for t
he increased extracellular matrix seen in cirrhosis. The cytokine oncostati
n M has been implicated in fibrogenesis in vitro in other cell types and in
vice in other tissues, although its effect on hepatic stellate cells or in
cirrhosis is unknown,
Methods: To examine the effect of oncostatin M on collagen production by hu
man hepatic stellate cells in culture, collagen protein was measured and co
llagen alpha 2(1) mRNA was quantified by Northern analysis. Tissue inhibito
r of metalloproteinase-1 (an inhibitor of collagen degradation) mRNA was me
asured in response to oncostation M stimulation, To explore the potential b
iological significance of this work to human liver disease, oncostatin M me
ssenger RNA in normal and cirrhotic human liver was measured.
Results: Oncostatin M induced in a 2-fold increase in collagen secretion. T
he potency of induction of collagen protein secretion was equal to that obs
erved after transforming growth factor beta stimulation. An increase in end
ogenous collagen alpha 2(1) mRNA could not be detected. This suggested a po
st-transcriptional mechanism for the increase in collagen protein. In respo
nse to oncostatin M stimulation, there was a 2-fold increase in the tissue
inhibitor or metalloproteinase-1 mRNA. Oncostatin M mRNA was detected in 6/
6 cirrhotic livers and 1/7 normal livers after 28 PCR cycles,
Conclusion: These results suggest that oncostatin M expression is upregulat
ed in cirrhosis where it may have a role as a profibrogenic cytokine in hep
atic stellate cells.