The balancing act of the liver: tissue regeneration versus fibrosis
Lucía Cordero-Espinoza, Meritxell Huch
Lucía Cordero-Espinoza, Meritxell Huch
Published January 2, 2018
Citation Information: J Clin Invest. 2018;128(1):85-96. https://doi.org/10.1172/JCI93562.
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The balancing act of the liver: tissue regeneration versus fibrosis

Abstract

Epithelial cell loss alters a tissue’s optimal function and awakens evolutionarily adapted healing mechanisms to reestablish homeostasis. Although adult mammalian organs have a limited regeneration potential, the liver stands out as one remarkable exception. Following injury, the liver mounts a dynamic multicellular response wherein stromal cells are activated in situ and/or recruited from the bloodstream, the extracellular matrix (ECM) is remodeled, and epithelial cells expand to replenish their lost numbers. Chronic damage makes this response persistent instead of transient, tipping the system into an abnormal steady state known as fibrosis, in which ECM accumulates excessively and tissue function degenerates. Here we explore the cellular and molecular switches that balance hepatic regeneration and fibrosis, with a focus on uncovering avenues of disease modeling and therapeutic intervention.

Authors

Lucía Cordero-Espinoza, Meritxell Huch

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Figure 2

Periodicity of damage alters the ability of the tissue to return to homeostasis.

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Periodicity of damage alters the ability of the tissue to return to home...
(Left) In healthy individuals, a punctual tissue injury (injury 1) to the liver awakens a regenerative response (green curve) to reestablish homeostasis or steady-state. Repeated injuries (injuries 1 + 2) hinder regeneration and make the system drift into a diseased state known as fibrosis (red curve). The tissue may recover from this as time progresses if no further damage is applied (resolution, injuries 1 + 2 + time, yellow curve). Alternatively, fibrosis will be maintained in the face of new damage (injuries 1+2+3, red curve). Additional injuries deteriorate the tissue until it reaches a cirrhotic (1 + 2 + 3 + 4, light purple curve) or advanced cirrhotic (1 + 2 + 3 + 4 + 5, dark purple curve) state. Recovery from this latter scenario is very unlikely. (Right) The tissue of predisposed individuals (e.g., aged) functions at an abnormal steady-state that makes them prone to develop fibrosis, thus accelerating disease progression and reaching a point of no recovery earlier.