Alcohol, Signaling, and ECM Turnover
Article first published online: 23 OCT 2009
Copyright © 2009 by the Research Society on Alcoholism. No claim to original U.S. government works
Alcoholism: Clinical and Experimental Research
Volume 34, Issue 1, pages 4–18, January 2010
How to Cite
Seth, D., D’Souza El-Guindy, N. B., Apte, M., Mari, M., Dooley, S., Neuman, M., Haber, P. S., Kundu, G. C., Darwanto, A., De Villiers, W. J., Vonlaufen, A., Xu, Z., Phillips, P., Yang, S., Goldstein, D., Pirola, R. M., Wilson, J. S., Moles, A., Fernández, A., Colell, A., García-Ruiz, C., Fernández-Checa, J. C., Meyer, C. and Meindl-Beinker, N. M. (2010), Alcohol, Signaling, and ECM Turnover. Alcoholism: Clinical and Experimental Research, 34: 4–18. doi: 10.1111/j.1530-0277.2009.01060.x
- Issue published online: 17 DEC 2009
- Article first published online: 23 OCT 2009
- Received for publication June 3, 2009; accepted August 20, 2009.
- Liver Disease;
- Bacterial and Viral Infection
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.