Oxidative and nitrosative stress and fibrogenic response.
Uncontrolled production of collagen I is the main feature of liver fibrosis. Following a fibrogenic stimulus such as alcohol, hepatic stellate cells (HSC) transform into an activated collagen-producing cell. In alcoholic liver disease, numerous changes in gene expression are associated with HSC activation, including the induction of several intracellular signaling cascades, which help maintain the activated phenotype and control the fibrogenic and proliferative state of the cell. Detailed analyses for understanding the molecular basis of the collagen I gene regulation have revealed a complex process involving reactive oxygen species (ROS) as key mediators. Less is known, however, about the contribution of reactive nitrogen species (RNS). In addition, a series of cytokines, growth factors, and chemokines, which activate extracellular matrix (ECM)-producing cells through paracrine and autocrine loops, contribute to the fibrogenic response.
Urtasun
R
R
Mount Sinai School of Medicine, Department of Medicine/Division of Liver Diseases, New York, NY 10029, USA.
Conde de la Rosa
L
L
Nieto
N
N
D019898:Autocrine Communication; D024042:Collagen Type I / Q000235:genetics / Q000378:metabolism*; D005109:Extracellular Matrix / Q000378:metabolism; D005786:Gene Expression Regulation; D055166:Hepatic Stellate Cells / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008103:Liver Cirrhosis / Q000378:metabolism* / Q000473:pathology; D008104:Liver Cirrhosis, Alcoholic / Q000378:metabolism; D045726:Metalloproteases / Q000378:metabolism; D018384:Oxidative Stress; D019899:Paracrine Communication; D026361:Reactive Nitrogen Species / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction
D024042:Collagen Type I; D026361:Reactive Nitrogen Species; D017382:Reactive Oxygen Species; D045726:Metalloproteases