Life sciences · 2026
Transcriptional and post-transcriptional activation of GATA4 contributes to liver regeneration.
СтатьяНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Miao Xiulian, Dong Wenhui, Zhou Jiawen, Wu Meng, Gong Shanwen, Xu Yiwen
Аннотация
AIMS: Hepatocytes can resume proliferation to replenish the loss of liver mass following liver injury in a process known as liver regeneration. In the present study we investigated the role of GATA4, a zinc finger-containing transcription factor, in this process.
METHODS AND MATERIALS: Liver regeneration was modeled in vitro by treating primary hepatocytes with hepatocytes growth factor (HGF). Liver regeneration was modeled in mice subjected to partial hepatectomy (PHx) or acetaminophen (APAP) injection.
KEY FINDINGS: We report that GATA4 expression was up-regulated in hepatocytes at both transcriptional and post-translational levels during liver regeneration. c-Jun bound to the Gata4 promoter and activated Gata4 transcription. In addition, the ubiquitin E3 ligase Cullin 4a (Cul4a) interacted with GATA4 to promote its degradation; down-regulation of Cul4a enabled GATA4 stabilization and accumulation. GATA4 knockdown attenuated HGF-induced proliferation of hepatocytes in vitro and weakened liver regeneration following PHx or APAP injection in mice. Importantly, GATA4 expression was detected to be positively correlated with proliferation of hepatocytes and inversely correlated with liver injury in patients with acute liver failure.
SIGNIFICANCE: Our data unveil a novel role of GATA4 in liver regeneration and its implication in acute liver failure.
METHODS AND MATERIALS: Liver regeneration was modeled in vitro by treating primary hepatocytes with hepatocytes growth factor (HGF). Liver regeneration was modeled in mice subjected to partial hepatectomy (PHx) or acetaminophen (APAP) injection.
KEY FINDINGS: We report that GATA4 expression was up-regulated in hepatocytes at both transcriptional and post-translational levels during liver regeneration. c-Jun bound to the Gata4 promoter and activated Gata4 transcription. In addition, the ubiquitin E3 ligase Cullin 4a (Cul4a) interacted with GATA4 to promote its degradation; down-regulation of Cul4a enabled GATA4 stabilization and accumulation. GATA4 knockdown attenuated HGF-induced proliferation of hepatocytes in vitro and weakened liver regeneration following PHx or APAP injection in mice. Importantly, GATA4 expression was detected to be positively correlated with proliferation of hepatocytes and inversely correlated with liver injury in patients with acute liver failure.
SIGNIFICANCE: Our data unveil a novel role of GATA4 in liver regeneration and its implication in acute liver failure.