API

Relationship: 1789

Title

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Necrotic Tissue leads to Liver Injury

Upstream event

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Necrotic Tissue

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
Mitochondrial complex inhibition leading to liver injury adjacent High High
IKK complex inhibition leading to liver injury adjacent High High

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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Logically when liver tissue is degraded, the liver will fail to execute its function. Again, this can be tissue type dependent(Krishna 2017)

Evidence Supporting this KER

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Biological Plausibility

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Necrotic tissue is frequently observed in liver disease, e.g. a failing liver.

Reviews:

(Guicciardi et al. 2013): Apoptosis and necrosis in the liver.

(Luedde et al. 2014): Cell death in liver disease.

(Krishna 2017): Patterns of Necrosis in Liver disease.

(Malhi et al. 2006): Apoptosis and necrosis in the liver (including TNF signaling (NFkB and Caspase8) part)

Empirical Evidence

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Uncertainties and Inconsistencies

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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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Krishna, M., 2017. Patterns of Necrosis in Liver Disease. , 10(2), pp.53–56.

Guicciardi, M.E. et al., 2013. Apoptosis and Necrosis in the Liver. Comprehensive Physiology, 3(2), pp.977–1010. Available at: http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=3867948&tool=pmcentrez&rendertype=abstract.

Luedde, T., Kaplowitz, N. & Schwabe, R.F., 2014. Cell Death and Cell Death Responses in Liver Disease: Mechanisms and Clinical Relevance. Gastroenterology., 14(11), pp.871–882.

Malhi, H., Gores, G.J. & Lemasters, J.J., 2006. Apoptosis and necrosis in the liver: A tale of two deaths? Hepatology, 43(2 SUPPL. 1), pp.31–44.