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


The Hedgehog (Hh) and Wnt/beta-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. The Wnt/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.


PubMed ID: 31875560

Projects: Early Metabolic Injury (LiSyM-EMI - Pillar I)

Publication type: Journal

Journal: Cell Rep

Citation: Cell Rep. 2019 Dec 24;29(13):4553-4567.e7. doi: 10.1016/j.celrep.2019.11.104.

Date Published: 24th Dec 2019

Registered Mode: by PubMed ID

Authors: E. Kolbe, S. Aleithe, C. Rennert, L. Spormann, F. Ott, D. Meierhofer, R. Gajowski, C. Stopel, S. Hoehme, M. Kucken, L. Brusch, M. Seifert, W. von Schoenfels, C. Schafmayer, M. Brosch, U. Hofmann, G. Damm, D. Seehofer, J. Hampe, R. Gebhardt, M. Matz-Soja

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Created: 27th Nov 2020 at 17:39

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