Molecular therapy for hepatic injury and fibrosis: where are we?
Hepatic fibrosis is a wound healing response, involving pathways of inflammation and fibrogenesis. In response to various insults, such as alcohol, ischemia, viral agents, and medications or hepatotoxins, hepatocyte damage will cause the release of cytokines and other soluble factors by Kupffer cells and other cell types in the liver. These factors lead to activation of hepatic stellate cells, which synthesize large amounts of extracellular matrix components. With chronic injury and fibrosis, liver architecture and metabolism are disrupted, eventually manifesting as cirrhosis and its complications. In addition to eliminating etiology, such as antiviral therapy and pharmacological intervention, it is encouraging that novel strategies are being developed to directly address hepatic injury and fibrosis at the subcellular and molecular levels. With improvement in understanding these mechanisms and pathways, key steps in injury, signaling, activation, and gene expression are being targeted by molecular modalities and other molecular or gene therapy approaches. This article intends to provide an update in terms of the current status of molecular therapy for hepatic injury and fibrosis and how far we are from clinical utilization of these new therapeutic modalities.
Prosser
Colette C
CC
Yen
Roy D
RD
Wu
Jian
J
D000818:Animals; D017209:Apoptosis; D005109:Extracellular Matrix / Q000502:physiology; D015316:Genetic Therapy; D006801:Humans; D008103:Liver Cirrhosis / Q000628:therapy*; D020784:Matrix Metalloproteinase 8 / Q000235:genetics; D016376:Oligonucleotides, Antisense / Q000627:therapeutic use; D017346:Protein Serine-Threonine Kinases; D017382:Reactive Oxygen Species; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000037:antagonists & inhibitors / Q000235:genetics; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics; D013482:Superoxide Dismutase / Q000235:genetics; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000235:genetics
D016376:Oligonucleotides, Antisense; D017382:Reactive Oxygen Species; D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D013482:Superoxide Dismutase; D020797:Receptor, Platelet-Derived Growth Factor beta; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II; D020784:Matrix Metalloproteinase 8