Extracellular matrix and liver disease.
CONCLUSIONS
The extracellular matrix (ECM) is a dynamic microenvironment that undergoes continuous remodeling, particularly during injury and wound healing. Chronic liver injury of many different etiologies such as viral hepatitis, alcohol abuse, drug-induced liver injury, obesity and insulin resistance, metabolic disorders, and autoimmune disease is characterized by excessive deposition of ECM proteins in response to persistent liver damage.


RESULTS
This review describes the main collagenous and noncollagenous components from the ECM that play a significant role in pathological matrix deposition during liver disease. We define how increased myofibroblasts (MF) from different origins are at the forefront of liver fibrosis and how liver cell-specific regulation of the complex scarring process occurs.


BACKGROUND
Particular attention is paid to the role of cytokines, growth factors, reactive oxygen species, and newly identified matricellular proteins in the regulation of fibrillar type I collagen, a field to which our laboratory has significantly contributed over the years. We compile data from recent literature on the potential mechanisms driving fibrosis resolution such as MF' apoptosis, senescence, and reversal to quiescence.


CONCLUSIONS
We conclude with a brief description of how epigenetics, an evolving field, can regulate the behavior of MF and of how new "omics" tools may advance our understanding of the mechanisms by which the fibrogenic response to liver injury occurs.
1 Division of Liver Diseases, Department of Medicine, Mount Sinai School of Medicine , New York, New York.
Elena
E
Arriazu
Marina
M
Ruiz de Galarreta
Francisco Javier
FJ
Cubero
Marta
M
Varela-Rey
María Pilar
MP
Pérez de Obanos
Tung Ming
TM
Leung
Aritz
A
Lopategi
Aitor
A
Benedicto
Ioana
I
Abraham-Enachescu
Natalia
N
Nieto
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D005109:Extracellular Matrix / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008107:Liver Diseases / Q000378:metabolism* / Q000473:pathology*; D058628:Myofibroblasts / Q000378:metabolism / Q000473:pathology