title: A systems biology approach for understanding the collagen regulatory network in alcoholic liver disease.
abstract: Among the pathogenesis and risk factors of alcoholic liver disease (ALD) are the source of dietary fat, obesity, insulin resistance, adipokines and acetaldehyde. Translocation of Gram-negative bacteria from the gut, the subsequent effects mediated by endotoxin, and the increased production of matricellular proteins, cytokines, chemokines and growth factors, actively participate in the progression of liver injury. In addition, generation of reactive oxygen and nitrogen species and the activation of non-parenchymal cells also contribute to the pathophysiology of ALD. A key event leading to liver damage is the transition of quiescent hepatic stellate cells into activated myofibroblasts, with the consequent deposition of fibrillar collagen I resulting in significant scarring. Thus, it is becoming clearer that matricellular proteins are critical players in the pathophysiology of liver disease; however, additional mechanistic insight is needed to understand the signalling pathways involved in the up-regulation of collagen I protein. At present, systems biology approaches are helping to answer the many unresolved questions in this field and are allowing to more comprehensively identify protein networks regulating pathological collagen I deposition in hopes of determining how to prevent the onset of liver fibrosis and/or to slow disease progression. Thus, this review article provides a snapshot on current efforts for identifying pathological protein regulatory networks in the liver using systems biology tools. These approaches hold great promise for future research in liver disease.
authors: Department of Medicine, Division of Liver Diseases, Mount Sinai School of Medicine, New York, NY 10029, USA. natalia.nieto@mssm.edu
authors: Natalia
authors: N
authors: Nieto
mesh_terms: D054338:Cell Transdifferentiation; D003094:Collagen / Q000235:genetics* / Q000378:metabolism; D020869:Gene Expression Profiling; D053263:Gene Regulatory Networks; D055166:Hepatic Stellate Cells / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008108:Liver Diseases, Alcoholic / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D058628:Myofibroblasts / Q000378:metabolism / Q000473:pathology; D060066:Protein Interaction Maps; D049490:Systems Biology
chemical_list: D003094:Collagen