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Genome-wide changes in OGT-deficient mouse liver tissue

ABSTRACT: Over a billion people suffer from chronic liver diseases worldwide, which often leads to fibrosis and then cirrhosis. Treatments for fibrosis remain experimental, in part because no unifying mechanism has been identified that initiates liver fibrosis. O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT) plays a pro-survival role under stress in many tissues. Here we report that OGT protects against hepatocyte necroptosis and initiation of liver fibrosis. Decreased O-GlcNAc levels were seen in patients with alcoholic liver cirrhosis and in mice with ethanol-induced liver injury. Liver-specific O-GlcNAc transferase (OGT) knockout (OGT-LKO) mice progressed to liver fibrosis at 10 weeks of age. OGT-deficient hepatocytes underwent necroptosis. These findings identify OGT as a key suppressor of hepatocyte necroptosis and OGT-LKO mice may serve as an effective spontaneous genetic model of liver fibrosis.

ORGANISM(S): Mus musculus

PROVIDER: GSE134993 | GEO | 2019/11/04

REPOSITORIES: GEO

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O-GlcNAc transferase acts as a critical nutritional node for the control of liver homeostasis

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