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  • IN BRIEF

NUAK1 inhibition prevents fibrosis

  1. Sarah Crunkhorn
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Growing evidence suggests significant crosstalk between TGF-β and the Hippo pathway effectors YAP and TAZ in the regulation of tissue fibrosis. By analysing fibrotic human kidney biopsies and mouse tissues, Zhang et al. now identify the kinase NUAK1 as a critical TGF-β-induced activator of YAP in fibroblasts, which acts in concert with TGF-β/SMAD signalling to promote organ fibrogenesis. Activation of YAP and TAZ in fibroblasts further induces NUAK1 expression, creating a profibrotic positive feedback loop. In mouse models, fibroblast-specific NUAK1 deletion or treatment with the NUAK inhibitor HTH-02-006 protected against fibrosis of multiple organs; the inhibitor also reduced established kidney fibrosis in mice.

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Nature Reviews Drug Discovery 21, 338 (2022)

doi: https://doi.org/10.1038/d41573-022-00059-5

References

  1. Zhang, T. et al. NUAK1 promotes organ fibrosis via YAP and TGF-β/SMAD signalling. Sci. Transl Med. 14, eaaz4028 (2022)

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