Alcohol, Signaling, and ECM Turnover |
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| Authors: | Devanshi Seth,Nympha B. D'Souza El-Guindy,Minoti Apte,Montserrat Mari,Steven Dooley,Manuela Neuman,Paul S. Haber,Gopal C. Kundu,Agus Darwanto,Willem J. de Villiers,A. Vonlaufen,Z. Xu,P. Phillips,S. Yang,D. Goldstein,R. M. Pirola,J. S. Wilson,Anna Moles,Anna Ferná ndez,Anna Colell,Carmen Garcí a-Ruiz,José C. Ferná ndez-Checa,Christoph Meyer, Nadja M. Meindl-Beinker |
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| Affiliation: | From the Drug Health Services &Centenary Institute (DS, PSH), Royal Prince Alfred Hospital, Camperdown, NSW, Australia;Department of Internal Medicine (NBDE-G, AD, WJV), University of Kentucky and Veterans Affairs Medical Center, Lexington, Kentucky;Pancreatic Research Group (MA, AV, ZX, PP, SY, DG, RMP, JSW), South Western Sydney Clinical School, Wallace Wurth Building, The University of New South Wales, Sydney, Australia;Liver Unit and CIBEK (MM, AM, AF, AC, CG-R, JCF-C), IMDiM, Hospital Clínic i Provincial, CIBEREHD, IDIBAPS, Instituto Investigaciones Biomédicas de Barcelona, Consejo Superior de Investigaciones Científicas, Barcelona, Spain;Molecular Alcohol Research in Gastroenterology (SD, CM, NMM-B), II. Medical Clinic, Universitätsmedizin Mannheim, Medizinische Fakultät Mannheim der Ruprecht-Karls-Universität Heidelberg, Mannheim, Germany;In Vitro Drug Safety and Biotechnology and Department of Pharmacology (MN), Faculty of Medicine, University of Toronto, Ontario, Canada;and National Centre for Cell Science (GCK), Pune, Maharashtra, India. |
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| Abstract: | Alcohol is recognized as a direct hepatotoxin, but the precise molecular pathways that are important for the initiation and progression of alcohol-induced tissue injury are not completely understood. The current understanding of alcohol toxicity to organs suggests that alcohol initiates injury by generation of oxidative and nonoxidative ethanol metabolites and via translocation of gut-derived endotoxin. These processes lead to cellular injury and stimulation of the inflammatory responses mediated through a variety of molecules. With continuing alcohol abuse, the injury progresses through impairment of tissue regeneration and extracellular matrix (ECM) turnover, leading to fibrogenesis and cirrhosis. Several cell types are involved in this process, the predominant being stellate cells, macrophages, and parenchymal cells. In response to alcohol, growth factors and cytokines activate many signaling cascades that regulate fibrogenesis. This mini-review brings together research focusing on the underlying mechanisms of alcohol-mediated injury in a number of organs. It highlights the various processes and molecules that are likely involved in inflammation, immune modulation, susceptibility to infection, ECM turnover and fibrogenesis in the liver, pancreas, and lung triggered by alcohol abuse. |
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| Keywords: | Fibrosis Liver Disease Pancreas Lung Bacterial and Viral Infection |
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