Tumor necrosis factor alpha inhibits collagen alpha 1(I) gene expression in rat hepatic stellate cells through a G protein
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Updated: Jun 22, 2026

Isolation of Rat Portal Fibroblasts by In situ Liver Perfusion
Published on: June 29, 2012
I Hernández-Muñoz1, P de la Torre, J A Sánchez-Alcázar
1Servicio de Gastroenterologia, Hospital Universitario Doce de Octubre, Universidad Complutense, Madrid, Spain.
Background & Aims:
Tumor necrosis factor alpha (TNF-alpha) inhibits collagen gene expression in cultured fibroblasts. By binding to cell surface receptors, TNF-alpha promotes signals within the cells. The purpose of this study was to investigate the role played by G proteins in TNF-alpha-induced inhibition of collagen gene expression.
Methods:
Effect of TNF-alpha on collagen alpha 1(I) messenger RNA (mRNA) level was measured in cultured hepatic stellate cells in basal condition and after inhibiting or activating G proteins or the major intracellular signal transduction pathways.
Results:
TNF-alpha significantly decreased the level of alpha 1(I) collagen mRNA. Treatment of cells with pertussis toxin inhibited this effect, whereas blocking adenylate cyclase or protein kinase A had no effect. Likewise, blocking phospholipase A2, phospholipase C1 calcium channels, calmodulin, or protein kinase C did not eliminate the inhibitory effect of TNF-alpha on collagen mRNA. On the other hand, C2-ceramide and sphingomyelinase reproduced the effect of TNF-alpha on collagen gene expression, and TNF-alpha did not increase the effect of sphingomyelinase.
Conclusions:
TNF-alpha-induced inhibition of alpha 1(I) collagen gene expression in a hepatic stellate cell line may be mediated by a pertussis toxin-sensitive G protein. TNF-alpha may inhibit this gene by using sphingomyelin/ceramide as an intracellular signal transduction pathway.
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