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The balancing act of the liver: tissue regeneration versus fibrosis

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Cordero-Espinoza, Lucía 
Huch, Meritxell 


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.



Animals, Extracellular Matrix, Humans, Liver, Liver Cirrhosis, Liver Regeneration, Stromal Cells

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Journal of Clinical Investigation

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American Society for Clinical Investigation
Wellcome Trust (092096/B/10/Z)
Wellcome Trust (104151/Z/14/Z)
LCE is jointly funded by a Wellcome Trust Four-Year PhD Studentship with the Stem Cell Biology and Medicine Programme and a Wellcome Cambridge Trust Scholarship. MH is a Wellcome Trust Sir Henry Dale Fellow and is jointly funded by the Wellcome Trust and the Royal Society (104151/Z/14/Z). This work is partially funded by an H2020 grant awarded to MH (LSMF4LIFE).