Mechanisms of Liver Injury

Research output: Chapter in Book/Report/Conference proceedingChapter

1 Citation (Scopus)

Abstract

The death of constituent cell populations of the liver is a central component of liver injury cascades. Hepatocytes are targeted by most injurious stimuli, though other cells types are affected as well. Cell death in the liver can occur via apoptosis or necrosis. Apoptosis can be initiated via death receptor-mediated pathways, the extrinsic pathway, or from intracellular perturbations, the intrinsic pathway. Mitochondrial permeabilization is required for hepatocyte apoptosis, and both intrinsic and extrinsic pathways converge on mitochondria. Effector caspases are activated downstream of mitochondria, and cleave several cellular targets to result in the characteristic apoptotic morphology. Dead cells release damage-associated molecular patterns that activate the innate immune system and downstream inflammatory cascades. Ongoing apoptosis in the liver stimulates Kupffer cells, and activates hepatic stellate cell-stimulating fibrosis. Therapies aimed at preventing hepatocyte apoptosis show promise in experimental and clinical settings.

Original languageEnglish (US)
Title of host publicationSchiff's Diseases of the Liver
PublisherWiley-Blackwell
Pages216-231
Number of pages16
ISBN (Print)0470654686, 9780470654682
DOIs
StatePublished - Oct 31 2011

Fingerprint

Apoptosis
Liver
Wounds and Injuries
Hepatocytes
Mitochondria
Cell Death
Effector Caspases
Hepatic Stellate Cells
Death Domain Receptors
Kupffer Cells
Immune System
Fibrosis
Necrosis
Population
Therapeutics

Keywords

  • Apoptosis
  • Caspase
  • Fas
  • Liver injury
  • Mitochondrial permeabilization
  • Necrosis
  • TRAIL
  • Tumor necrosis factor α (TNF-α)

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Malhi, H. M., & Gores, G. J. (2011). Mechanisms of Liver Injury. In Schiff's Diseases of the Liver (pp. 216-231). Wiley-Blackwell. https://doi.org/10.1002/9781119950509.ch8

Mechanisms of Liver Injury. / Malhi, Harmeet M; Gores, Gregory James.

Schiff's Diseases of the Liver. Wiley-Blackwell, 2011. p. 216-231.

Research output: Chapter in Book/Report/Conference proceedingChapter

Malhi, HM & Gores, GJ 2011, Mechanisms of Liver Injury. in Schiff's Diseases of the Liver. Wiley-Blackwell, pp. 216-231. https://doi.org/10.1002/9781119950509.ch8
Malhi HM, Gores GJ. Mechanisms of Liver Injury. In Schiff's Diseases of the Liver. Wiley-Blackwell. 2011. p. 216-231 https://doi.org/10.1002/9781119950509.ch8
Malhi, Harmeet M ; Gores, Gregory James. / Mechanisms of Liver Injury. Schiff's Diseases of the Liver. Wiley-Blackwell, 2011. pp. 216-231
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