Abbreviations:4-HNE (4-hydroxynonenal), AAV (adeno-associated virus), ACAA2 (3-ketoacyl CoA thiolase), AH (alcoholic hepatitis), ALD (alcoholic liver disease), ALT (alanine aminotransferase), AST (aspartate aminotransferase), Bak (Bcl-2 homologous antagonist killer), BAP31 (B-cell receptor-associated protein 31), Bax (Bcl-2-associated X protein), CRT (calreticulin), CXCL10 (C-X-C chemokine ligand 10), DAMP (damage-associated molecular pattern), EIF2S1 (eukaryotic transcription factor 2 subunit 1), ER (endoplasmic reticulum), IL-1 β (interleukin 1 beta), MCP1 (monocyte chemoattractant protein 1), MCS-F (macrophage colony-stimulating factor), NAD+ (oxidized nicotinamide adenine dinucleotide), NADH (reduced nicotinamide adenine dinucleotide), ROS (reactive oxygen species), RTK (receptor tyrosine kinase), Shc (Src homology and collagen), ShcKD (Shc knockdown/Shc hypomorph), ShcHepKO (hepatocyte-specific Shc knockout), TG (triglyceride)
Publication stageIn Press Journal Pre-Proof
The authors have declared that no conflict of interest exists.
Funding Information: VA Merit award I01 BX002418 and 5RO1AG060726 (NJT, and GC).
Synopsis: We describe the role of Src homology and collagen proteins in alcoholic steatohepatitis. p46 Shc mediates lipid peroxidation, oxidative stress, and calreticulin translocation to the membrane where it acts as DAMP. Shc inhibition reduces inflammation in alcoholic liver injury.
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