Intracellular signaling pathways in stellate cell activation.
Pathological fibrogenesis in the liver is mediated by activated stellate cells. These cells have a myofibroblastic phenotype with the ability to proliferate and synthesize large quantities of extracellular matrix components. A number of factors have been proposed to initiate and perpetuate the fibrogenic process in stellate cells, including inflammatory cytokines, alterations in the extracellular matrix, growth factors, and oxidative stress. Some recent research has focused on the intracellular signaling pathways that are stimulated by these factors in stellate cells, including mitogen-activated protein kinases, phosphatidylinositol 3-kinase, focal adhesion kinase, and protein kinase C. This paper will summarize the experimental evidence that implicates these pathways in stellate cell activation, focusing on the effects of exposure to platelet-derived growth factor, tumor necrosis factor-alpha, and fibronectin. Implications for alcohol-induced hepatic fibrosis and future directions for research will also be discussed.
Britton
R S
RS
Department of Internal Medicine, Saint Louis University School of Medicine, Missouri 63110, USA. brittonr@wpogate.slu.edu
Bacon
B R
BR
D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000276:immunology / Q000502:physiology*; D015815:Cell Adhesion Molecules / Q000276:immunology / Q000502:physiology; D005109:Extracellular Matrix / Q000502:physiology; D005353:Fibronectins / Q000502:physiology; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; D006801:Humans; D007728:Kupffer Cells / Q000276:immunology / Q000502:physiology*; D008099:Liver / Q000166:cytology / Q000276:immunology; D008103:Liver Cirrhosis / Q000276:immunology / Q000503:physiopathology; D010982:Platelet-Derived Growth Factor / Q000276:immunology / Q000502:physiology; D011493:Protein Kinase C / Q000276:immunology / Q000502:physiology; D011505:Protein-Tyrosine Kinases / Q000276:immunology / Q000502:physiology; D011972:Receptor, Insulin / Q000276:immunology / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology
D015815:Cell Adhesion Molecules; D005353:Fibronectins; D010982:Platelet-Derived Growth Factor; D014409:Tumor Necrosis Factor-alpha; D011505:Protein-Tyrosine Kinases; D011972:Receptor, Insulin; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; C496050:PTK2 protein, human; D011493:Protein Kinase C; D017871:Calcium-Calmodulin-Dependent Protein Kinases