TGFβ inhibition restores a regenerative response in acute liver injury by suppressing paracrine senescence.

ABSTRACT: Liver injury results in rapid regeneration through hepatocyte proliferation and hypertrophy. However, after acute severe injury, such as acetaminophen poisoning, effective regeneration may fail. We investigated how senescence may underlie this regenerative failure. In human acute liver disease, and murine models, p21-dependent hepatocellular senescence was proportionate to disease severity and was associated with impaired regeneration. In an acetaminophen injury mouse model, a transcriptional signature associated with the induction of paracrine senescence was observed within 24 hours and was followed by one of impaired proliferation. In mouse genetic models of hepatocyte injury and senescence, we observed transmission of senescence to local uninjured hepatocytes. Spread of senescence depen

SUBMITTER: Bird TG 

PROVIDER: S-EPMC6420144 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature