API

Relationship: 82

Title

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Accumulation, Collagen leads to N/A, Liver fibrosis

Upstream event

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Accumulation, Collagen

Downstream event

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N/A, Liver fibrosis

Key Event Relationship Overview

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AOPs Referencing Relationship

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AOP Name Directness Weight of Evidence Quantitative Understanding
Protein Alkylation leading to Liver Fibrosis directly leads to Strong

Taxonomic Applicability

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Term Scientific Term Evidence Link
human Homo sapiens Strong NCBI
Rattus norvegicus Rattus norvegicus Strong NCBI

Sex Applicability

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Life Stage Applicability

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How Does This Key Event Relationship Work

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Liver fibrosis is the excessive accumulation of extracellular matrix (ECM) proteins including collagen. Liver fibrosis results from an imbalance between the deposition and degradation of ECM and a change of ECM composition; the latter initiates several positive feedback pathways that further amplify fibrosis. With chronic injury, there is progressive substitution of the liver parenchyma by scar tissue. Deposition of collagen in the liver progressively disrupts the normal hepatic architecture so that the normal relationship between vascular inflow and outflow is destroyed and the normal collagen content around hepatic sinusoids in regenerating nodules becomes modified.Advanced liver fibrosis results in cirrhosis. [1] [2] [3] [4] [5] [6]

Weight of Evidence

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Biological Plausibility

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By definition, liver fibrosis is the excessive accumulation of ECM proteins that are produced by HSCs. The KER between this KE and the AO is undisputed. [1] [2] [4] [5] [6]

Empirical Support for Linkage

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There is a smooth transition from ECM accumulation to liver fibrosis without a definite threshold and plenty in vivo evidence exists that ECM accumulation is a pre-stage of liver fibrosis [1] [2] [4] [5] [6]

Uncertainties or Inconsistencies

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no inconsistencies

Quantitative Understanding of the Linkage

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no quantitative data

Evidence Supporting Taxonomic Applicability

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Human:[1] [2] [4] [5] [6] Rat: [7]

References

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  1. 1.0 1.1 1.2 1.3 Lee, U.E. and S.L. Friedman (2011), Mechanisms of Hepatic Fibrogenesis, Best Pract Res Clin Gastroenterol, vol. 25, no. 2, pp. 195-206.
  2. 2.0 2.1 2.2 2.3 Bataller, R. and D.A. Brenner (2005), Liver Fibrosis, J.Clin. Invest, vol. 115, no. 2, pp. 209-218.
  3. Pellicoro, A. et al. (2014), Liver fibrosis and repair: immune regulation of wound healing in a solid organ, Nat Rev Immunol, vol. 14, no. 3, pp. 181-194.
  4. 4.0 4.1 4.2 4.3 Brancatelli, G. et al. (2009), Focal confluent fibrosis in cirrhotic liver: natural history studied with serial CT, AJR Am J Roentgenol, vol. 192, no. 5, pp. 1341-1347.
  5. 5.0 5.1 5.2 5.3 Rockey, D.C. and S.L. Friedman (2006), Hepatic fibrosis and cirrhosis, Zakim and Boyer's Hepatology, 5th edition, section 1, chapter 6, pp. 87-109.
  6. 6.0 6.1 6.2 6.3 Poynard, T., P. Bedossa and P. Opolon (1997), Natural history of liver fibrosis progression in patients with chronic hepatitis C. The OBSVIRC, METAVIR, CLINIVIR, and DOSVIRC groups, Lancet, vol. 349, no. 9055, pp. 825-832.
  7. Liedtke, C. et al. (2013), Experimental liver fibrosis research: update on animal models, legal issues and translational aspects, Fibrogenesis Tissue Repair, vol. 6, no. 1, p. 19.