Research ArticleLiver disease

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

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Science Translational Medicine  15 Aug 2018:
Vol. 10, Issue 454, eaan1230
DOI: 10.1126/scitranslmed.aan1230

Setting liver regeneration free

The liver is an excellent model of organ regeneration; however, regeneration may fail in a normal liver after acute severe injury such as acetaminophen poisoning. Bird and colleagues now show that a process that prevents proliferation termed senescence, which is classically associated with aging and carcinogenesis, inhibits the liver’s regenerative cells after acute injury. This senescence can be spread from cell to cell by the signaling molecule transforming growth factor–β (TGFβ). When TGFβ signaling was blocked during acetaminophen poisoning in mice, senescence was impeded, regeneration accelerated, and mouse survival increased. Therefore, targeting senescence induced by acute tissue injury is an attractive therapeutic approach to improve regeneration.

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