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Regenerative medicine

Inhibiting prostaglandin breakdown triggers tissue regeneration

Nature Reviews Drug Discovery volume 14, pages 526–527 (2015)Cite this article

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The prostaglandin PGE2 is a lipid signalling molecule involved in the promotion of pain and inflammation. Therapeutic interventions to date have therefore focused on reducing PGE2 production. However, given that PGE2 has also been implicated in tissue maintenance and regeneration, Zhang et al. set out to explore whether pharmacologically increasing PGE2 levels might potentiate tissue repair in mice.

To do this, they focused on reducing levels of 15-PGDH, an enzyme responsible for catalysing prostaglandin breakdown. They first studied 15-PGDH-knockout mice and found PGE2 levels to be twofold higher in lung, colon, bone marrow and liver cells, compared to those of wild-type mice. Using a high-throughput screen of 230,000 synthetic compounds, they then identified the small molecule SW033291 as a potent inhibitor of 15-PGDH enzyme activity in vitro. Mice injected with SW033291 phenocopied 15-PGDH knockout mice, displaying similar increases in PGE2 levels across tissues, without signs of toxicity.

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References

  1. Zhang, Y. et al. Inhibition of the prostaglandin-degrading enzyme 15-PGDH potentiates tissue regeneration. Science 348, aaa2340 (2015)

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  1. Sarah Crunkhorn
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Crunkhorn, S. Inhibiting prostaglandin breakdown triggers tissue regeneration. Nat Rev Drug Discov 14, 526–527 (2015). https://doi.org/10.1038/nrd4690

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