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.
Seth
Devanshi
D
Drug Health Services & Centenary Institute, Royal Prince Alfred Hospital, Camperdown, NSW, Australia. devanshi.seth@email.cs.nsw.gov.au
D'Souza El-Guindy
Nympha B
NB
Apte
Minoti
M
Mari
Montserrat
M
Dooley
Steven
S
Neuman
Manuela
M
Haber
Paul S
PS
Kundu
Gopal C
GC
Darwanto
Agus
A
de Villiers
Willem J
WJ
Vonlaufen
A
A
Xu
Z
Z
Phillips
P
P
Yang
S
S
Goldstein
D
D
Pirola
R M
RM
Wilson
J S
JS
Moles
Anna
A
Fernández
Anna
A
Colell
Anna
A
García-Ruiz
Carmen
C
Fernández-Checa
José C
JC
Meyer
Christoph
C
Meindl-Beinker
Nadja M
NM
D000437:Alcoholism / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D000431:Ethanol / Q000008:administration & dosage / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008108:Liver Diseases, Alcoholic / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction / Q000502:physiology*
D000431:Ethanol