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FIBROSIS

Danger! P2Y14 receptor links cell death to liver fibrosis

Nature Reviews Gastroenterology & Hepatology volume 19, page 349 (2022)Cite this article

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Dying hepatocytes release so-called danger signals that trigger inflammatory responses and removal of cellular debris. New research has revealed a cell death-induced profibrotic signal arising from P2Y14 ligands and their receptor that links cell death to fibrogenesis after liver injury in mice.

DAMP receptor screening identified the purinergic receptor P2Y14 as a candidate that was highly enriched in HSCs, a key cell type in liver fibrosis. Moreover, the P2Y14 ligands (uridine 5ʹ-diphosphate (UDP)-glucose, UDP-galactose and UDP-glucuronic acid) were enriched in hepatocytes and released upon cell death. Importantly, ligand–receptor interaction analysis confirmed P2Y14 ligands and receptor as a link between dying hepatocytes and HSCs, acting as a DAMP–DAMP receptor system.

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References

Original article

  • Mederacke, I. et al. The purinergic P2Y14 receptor links hepatocyte death to hepatic stellate cell activation and fibrogenesis in the liver. Sci. Transl Med. 14, eabe5795 (2022)

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  1. Nature Reviews Gastroenterology & Hepatology http://www.nature.com/nrgastro/

    Katrina Ray

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  1. Katrina Ray
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Correspondence to Katrina Ray.

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Ray, K. Danger! P2Y14 receptor links cell death to liver fibrosis. Nat Rev Gastroenterol Hepatol 19, 349 (2022). https://doi.org/10.1038/s41575-022-00621-x

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  • DOI: https://doi.org/10.1038/s41575-022-00621-x

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