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ASK1/ p38 axis inhibition blocks the release of mitochondrial "danger signals" from hepatocytes and suppresses progression to cirrhosis and liver cancer.

Zhenwei PengGuangyan WeiPinzhu HuangHeansika MattaWen GaoPing AnShuangshuang ZhaoYi LinLi TanKahini VaidDisha Skelton-BadlaniImad NasserGrant BudasDavid LopezLi LiDavid BreckenridgeRob MyersJohn McHutchisonMing KuangYury V Popov
Published in: Hepatology (Baltimore, Md.) (2024)
ASK1 inhibition suppresses the profibrogenic release of mitochondrial deoxyribonucleic acid from dying hepatocytes in a p38-dependent manner and protects from liver fibrosis. Long-term ASK1 targeting resulted in diminished net antifibrotic effect, but the progression to liver cirrhosis and cancer in BALBc/ Mdr2- / - mice was effectively inhibited. These data support the clinical evaluation of ASK1 inhibitors in fibrotic liver diseases.
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