Title:Identifying Novel Targets for Treatment of Liver Fibrosis: What Can We Learn from Injured Tissues which Heal Without a Scar?
Volume: 16
Issue: 12
Author(s): Michele T. Pritchard and Jennifer M. McCracken
Affiliation:
Keywords:
Extracellular matrix, fibrosis, hepatic stellate cell, inflammation, hyaluronan, macrophage.
Abstract: The liver is unique in that it is able to regenerate. This regeneration occurs without formation
of a scar in the case of non-iterative hepatic injury. However, when the liver is exposed to chronic
liver injury, the purely regenerative process fails and excessive extracellular matrix proteins are deposited
in place of normal liver parenchyma. While much has been discovered in the past three decades, insights
into fibrotic mechanisms have not yet lead to effective therapies; liver transplant remains the only
cure for advanced liver disease. In an effort to broaden the collection of possible therapeutic targets, this
review will compare and contrast the liver wound healing response to that found in two types of wound
healing: scarless wound healing of fetal skin and oral mucosa and scar-forming wound healing found in adult skin. This review
will examine wound healing in the liver and the skin in relation to the role of humoral and cellular factors, as well as the
extracellular matrix, in this process. While several therapeutic targets are similar between fibrotic liver and adult skin wound
healing, others are unique and represent novel areas for hepatic anti-fibrotic research. In particular, investigations into the role
of hyaluronan in liver fibrosis and fibrosis resolution are warranted.
