Role of Early Growth Response-1 in the Development of Alcohol-Induced Steatosis.
Here, we describe research on the involvement of the transcription factor, Early Growth Response- 1 (Egr-1) in alcohol-induced liver injury, specifically, fatty liver (steatosis), one of the earliest and most frequent signs of liver injury that occurs after heavy drinking. Egr-1 is a ubiquitous transcription factor found in nearly all cell types. However, because the liver is the principal site of ethanol oxidation, it sustains the greatest damage from alcohol abuse. Thus, this review focuses on how alcohol consumption causes changes in the hepatic expression of Egr-1, which, in turn causes downstream alterations in the expression of other genes to cause liver pathology. Ironically, while such changes in Egr-1 expression clearly favor steatosis and even fibrosis development, the absence of Egr-1 expression can actually exacerbate liver injury after excessive alcohol consumption or after exposure to other hepatotoxins. The existing literature on Egr-1 is extensive. Here, we confine our initial description of Egr-1 to its principal molecular characteristics, its biological functions, and its involvement in certain pathologies that are either directly or obliquely related to alcoholic liver disease. We describe experimental data that clearly implicate Egr-1 function in alcohol-induced steatosis and fibrosis, showing that ethanol-elicited regulation of Egr-1 expression depends on the generation of acetaldehyde and that the absence of Egr-1 diminishes alcohol-induced triglyceride accumulation. Overall, the existing evidence for the involvement of Egr-1 as a key link in alcohol-induced liver disease is strong. The evidence underscores the potential role of Egr-1 and several other transcription factors as therapeutic targets in the alleviation of alcoholic liver disease, which, even after decades of treatment options, still remains difficult to manage in the clinic.
Liver Study Unit, Research Service (151), Omaha Veterans Affairs Medical Center, 4101 Woolworth Avenue Omaha, NE 68501. 0.
Paul G
PG
Thomes
Liver Study Unit, Research Service (151), Omaha Veterans Affairs Medical Center, 4101 Woolworth Avenue Omaha, NE 68501. United States.
Terrence M
TM
Donohue
D000079:Acetaldehyde / Q000378:metabolism; D000818:Animals; D001343:Autophagy; D051766:Early Growth Response Protein 1 / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D008066:Lipolysis; D008108:Liver Diseases, Alcoholic / Q000378:metabolism* / Q000473:pathology; D015398:Signal Transduction
D051766:Early Growth Response Protein 1; D000079:Acetaldehyde
Egr-1; autophagy; ethanol; lipolysis; steatosis