Research ArticleFibrosis

Targeting acid ceramidase inhibits YAP/TAZ signaling to reduce fibrosis in mice

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Science Translational Medicine  19 Aug 2020:
Vol. 12, Issue 557, eaay8798
DOI: 10.1126/scitranslmed.aay8798

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Making a case for aCDase inhibition

Activation of YAP/TAZ mechanosignaling promotes organ fibrosis. Here, Alsamman et al. investigated acid ceramidase (aCDase) inhibition as a way to reduce liver fibrosis. Ceramide promoted YAP/TAZ degradation to inactivate human hepatic stellate cells (HSCs), and liver fibrosis was reduced in mice deficient in aCDase in HSCs. A ceramide analog inhibited aCDase, promoted YAP degradation, and blocked the progression of liver fibrosis in mice and in rodent and human precision liver slice explants. This study demonstrates how aCDase inhibition alters mechanosignaling in fibrosis and identifies a potential therapeutic target.

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