Mutual Zonated Interactions of Wnt and Hh Signaling Are Orchestrating the Metabolism of the Adult Liver in Mice and Human

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

Abstract

The Hedgehog (Hh) and Wnt/b-Catenin (Wnt) cascades are morphogen pathways whose pronounced influence on adult liver metabolism has been identified in recent years. How both pathways communicate and control liver metabolic functions are largely unknown. Detecting core components of Wnt and Hh signaling and mathematical modeling showed that both pathways in healthy liver act largely complementary to each other in the pericentral (Wnt) and the periportal zone (Hh) and communicate mainly by mutual repression. TheWnt/Hh module inversely controls the spatiotemporal operation of various liver metabolic pathways, as revealed by transcriptome, proteome, and metabolome analyses. Shifting the balance to Wnt (activation) or Hh (inhibition) causes pericentralization and periportalization of liver functions, respectively. Thus, homeostasis of the Wnt/Hh module is essential for maintaining proper liver metabolism and to avoid the development of certain metabolic diseases. With caution due to minor species-specific differences, these conclusions may hold for human liver as well.

Details

Original languageEnglish
Pages (from-to)4553-4567.e7
JournalCell Reports
Volume29
Issue number13
Publication statusPublished - 2019
Peer-reviewedYes

External IDs

Scopus 85076681304
ORCID /0000-0003-0137-5106/work/142244212
ORCID /0000-0002-2844-053X/work/153110476

Keywords

Sustainable Development Goals

Keywords

  • Liver Diseases