Research ArticleLIVER FIBROSIS

Hyaluronan synthase 2–mediated hyaluronan production mediates Notch1 activation and liver fibrosis

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Science Translational Medicine  12 Jun 2019:
Vol. 11, Issue 496, eaat9284
DOI: 10.1126/scitranslmed.aat9284

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HAlting liver fibrosis

Hepatic stellate cells (HSCs) play a key role in liver fibrosis, a process marked by the deposition of extracellular matrix including the glycosaminoglycan hyaluronan (HA). Here, Yang et al. investigated the mechanisms regulating HSCs and HA deposition using patient samples and mouse models. They found that HA synthase 2 was increased in HSCs in fibrotic patient and mouse liver tissues. HA and Notch1 signaling activated HSCs in an HA synthase 2–dependent process. Inhibiting HA synthesis reduced HSC activation and progression of liver fibrosis, identifying a therapeutic target.

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