NOX1-dependent redox signaling potentiates colonic stem cell proliferation to adapt to the intestinal microbiota by linking EGFR and TLR activation

Sjoerd van der Post, George M.H. Birchenough, Jason M. Held

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

Abstract

The colon epithelium is a primary point of interaction with the microbiome and is regenerated by a few rapidly cycling colonic stem cells (CSCs). CSC self-renewal and proliferation are regulated by growth factors and the presence of bacteria. However, the molecular link connecting the diverse inputs that maintain CSC homeostasis remains largely unknown. We report that CSC proliferation is mediated by redox-dependent activation of epidermal growth factor receptor (EGFR) signaling via NADPH oxidase 1 (NOX1). NOX1 expression is CSC specific and is restricted to proliferative CSCs. In the absence of NOX1, CSCs fail to generate ROS and have a reduced proliferation rate. NOX1 expression is regulated by Toll-like receptor activation in response to the microbiota and serves to link CSC proliferation with the presence of bacterial components in the crypt. The TLR-NOX1-EGFR axis is therefore a critical redox signaling node in CSCs facilitating the quiescent-proliferation transition and responds to the microbiome to maintain colon homeostasis.

Original languageEnglish
Article number108949
JournalCell Reports
Volume35
Issue number1
DOIs
StatePublished - Apr 6 2021

Keywords

  • EGFR
  • NADPH oxidases
  • NOX1
  • ROS
  • TLR
  • colon
  • microbiome
  • microbiota
  • redox signaling
  • stem cells

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