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Regulation of notch1 signaling by nrf2: implications for tissue regeneration

Nobunao Wakabayashi1, Soona Shin, Stephen L Slocum

  • 1Department of Environmental Health Sciences, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21205, USA. nw99@pitt.edu

Science Signaling
|July 15, 2010
PubMed

Insights

The Keap1-Nrf2-ARE pathway interacts with Notch1 signaling. Disrupting Nrf2 hinders liver regeneration, but Notch1 can restore this function.

Area of Science:

  • Cellular signaling pathways
  • Molecular biology
  • Hepatology

Background:

  • The Keap1-Nrf2-ARE pathway regulates cell survival against stress.
  • Keap1 normally degrades Nrf2 (nuclear factor erythroid-derived 2-related factor 2) in unstressed cells.
  • Cross-talk between signaling pathways is crucial for cellular adaptation.

Purpose of the Study:

  • To investigate the interaction between Keap1-Nrf2-ARE and Notch1 signaling.
  • To determine the role of Nrf2 in liver regeneration.
  • To explore Notch1's potential to rescue Nrf2-dependent processes.

Main Methods:

  • Transcriptional analyses in Keap1- or Nrf2-disrupted mice.
  • Identification of antioxidant response element (ARE) in Notch1 promoter.
  • Assessment of liver regeneration after partial hepatectomy.

Main Results:

  • Identified functional cross-talk between Keap1-Nrf2-ARE and Notch1 pathways.
  • Nrf2 was found to recognize a functional ARE in the Notch1 promoter.
  • Disruption of Nrf2 impaired liver regeneration, which was rescued by Notch1 reestablishment.

Conclusions:

  • Nrf2 and Notch1 signaling pathways functionally interact.
  • Nrf2 plays a critical role in liver regeneration.
  • Notch1 signaling can compensate for Nrf2 deficiency in liver regeneration.

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