Alcohol, signaling, and ECM turnover.


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.

DOI: 10.1111/j.1530-0277.2009.01060.x
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@article{Seth2010AlcoholSA, title={Alcohol, signaling, and ECM turnover.}, author={Devanshi Seth and Nympha B D'Souza El-Guindy and Minoti Vivek Apte and Montserrat Mar{\'i} and Steven Dooley and Manuela G. Neuman and Paul S. Haber and Gopal Chandra Kundu and Agus Darwanto and Willem J. S. de Villiers and Alain Vonlaufen and Zhi Xu and Phoebe A. Phillips and S Yang and Dita Goldstein and Roberto Pirola and Jeremy Somers Wilson and Anna Moles and Ana Fern{\'a}ndez and Anna Colell and Carmen Garc{\'i}a-Ruiz and Jos{\'e} C Fern{\'a}ndez-Checa and C. M. Meyer and Nadja M. Meindl-Beinker}, journal={Alcoholism, clinical and experimental research}, year={2010}, volume={34 1}, pages={4-18} }