Abstract:
:The Hedgehog (Hh) and Wnt/β-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.
journal_name
Cell Repjournal_title
Cell reportsauthors
Kolbe E,Aleithe S,Rennert C,Spormann L,Ott F,Meierhofer D,Gajowski R,Stöpel C,Hoehme S,Kücken M,Brusch L,Seifert M,von Schoenfels W,Schafmayer C,Brosch M,Hofmann U,Damm G,Seehofer D,Hampe J,Gebhardt R,Matz-Soja Mdoi
10.1016/j.celrep.2019.11.104subject
Has Abstractpub_date
2019-12-24 00:00:00pages
4553-4567.e7issue
13issn
2211-1247pii
S2211-1247(19)31604-3journal_volume
29pub_type
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