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.
Drug Health Services & Centenary Institute, Royal Prince Alfred Hospital, Camperdown, NSW, Australia. devanshi.seth@email.cs.nsw.gov.au
Devanshi
D
Seth
Nympha B
NB
D'Souza El-Guindy
Minoti
M
Apte
Montserrat
M
Mari
Steven
S
Dooley
Manuela
M
Neuman
Paul S
PS
Haber
Gopal C
GC
Kundu
Agus
A
Darwanto
Willem J
WJ
de Villiers
A
A
Vonlaufen
Z
Z
Xu
P
P
Phillips
S
S
Yang
D
D
Goldstein
R M
RM
Pirola
J S
JS
Wilson
Anna
A
Moles
Anna
A
Fernández
Anna
A
Colell
Carmen
C
García-Ruiz
José C
JC
Fernández-Checa
Christoph
C
Meyer
Nadja M
NM
Meindl-Beinker
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