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Regulation of Notch1 Signaling by Nrf2: Implications for Tissue Regeneration

Sci. Signal.  13 Jul 2010:
Vol. 3, Issue 130, pp. ra52
DOI: 10.1126/scisignal.2000762

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Setting the Pace of Regeneration

The ability of tissues to regenerate is critical for organismal survival, yet all of the mechanisms regulating this complex phenomenon are unknown. Nrf2 is a member of a family of transcription factors, and without the prosurvival signaling of Nrf2, mice are sensitive to oxidative and electrophilic stresses and exhibit delays in tissue regeneration. Wakabayashi et al. connect Nrf2 to the Notch signaling pathway, which is involved in determining cell proliferation and cell fate, by showing that Nrf2 transcriptionally stimulates expression of Notch1 to establish basal Notch1 signaling. The amount of Notch1 at the time of injury appears to set the pace of liver regeneration, and forced Notch signaling in hepatocytes restored liver regeneration in Nrf2-deficient mice.