API

Relationship: 1868

Title

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Activation, hepatic stellate cells leads to Liver Injury

Upstream event

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Activation, hepatic stellate cells

Downstream event

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Liver Injury

Key Event Relationship Overview

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AOPs Referencing Relationship

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AOP Name Adjacency Weight of Evidence Quantitative Understanding
Inhibition of N-linked glycosylation leads to liver injury adjacent Not Specified Not Specified

Taxonomic Applicability

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Sex Applicability

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Life Stage Applicability

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Key Event Relationship Description

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Stellate cell activation produces alterations in the extracellular matrix composition which lead to liver injury

Evidence Supporting this KER

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Biological Plausibility

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Apoptosis of hepatocytes from CHOP leads to Kupffer cell activation, which leads to induction of TGF-β1 expression. This in turn activates stellate cells and activation of inflammation response. This results in collagen accumulation and change in extracellular matrix composition in the liver causing fibrosis. (Vinken et al 2015, Ladesmann 2016) (Iracheta-Vellve et al., 2016)(Koo et al., 2016)(Guicciardi et al., 2013)

Empirical Evidence

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Uncertainties and Inconsistencies

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Inflamation response, not direct key event.

Quantitative Understanding of the Linkage

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Response-response Relationship

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Time-scale

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Known modulating factors

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Known Feedforward/Feedback loops influencing this KER

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Domain of Applicability

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References

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Guicciardi, M. E. et al. (2013) ‘Apoptosis and Necrosis in the Liver Maria’, Comprehensive Physiology, 3(2), pp. 977–1010. doi: 10.1002/cphy.c120020.Apoptosis.

Iracheta-Vellve, A. et al. (2016) ‘Endoplasmic reticulum stress-induced hepatocellular death pathways mediate liver injury and fibrosis via stimulator of interferon genes’, Journal of Biological Chemistry. doi: 10.1074/jbc.M116.736991.

Koo, J. H. et al. (2016) ‘Endoplasmic Reticulum Stress in Hepatic Stellate Cells Promotes Liver Fibrosis via PERK-Mediated Degradation of HNRNPA1 and Up-regulation of SMAD2’, Gastroenterology. Elsevier, Inc, 150(1), p. 181–193.e8. doi: 10.1053/j.gastro.2015.09.039.