Semin Liver Dis 2022; 42(01): 001-016
DOI: 10.1055/s-0041-1742279
Review Article

The Role of Liver Zonation in Physiology, Regeneration, and Disease

Regeant Panday
1   Department of Biomedical Engineering, University of Illinois at Chicago, Chicago, Illinois
,
Chase P. Monckton
1   Department of Biomedical Engineering, University of Illinois at Chicago, Chicago, Illinois
,
Salman R. Khetani
1   Department of Biomedical Engineering, University of Illinois at Chicago, Chicago, Illinois
› Author Affiliations
Funding C.P.M., R.P., and S.R.K. report grants: US NIH, 1R01DK115747–01A1.


Abstract

As blood flows from the portal triad to the central vein, cell-mediated depletion establishes gradients of soluble factors such as oxygen, nutrients, and hormones, which act through molecular pathways (e.g., Wnt/β-catenin, hedgehog) to spatially regulate hepatocyte functions along the sinusoid. Such “zonation” can lead to the compartmentalized initiation of several liver diseases, including alcoholic/non-alcoholic fatty liver diseases, chemical/drug-induced toxicity, and hepatocellular carcinoma, and can also modulate liver regeneration. Transgenic rodent models provide valuable information on the key molecular regulators of zonation, while in vitro models allow for subjecting cells to precisely controlled factor gradients and elucidating species–specific differences in zonation. Here, we discuss the latest advances in both in vivo and in vitro models of liver zonation and pending questions to be addressed moving forward. Ultimately, obtaining a deeper understanding of zonation can lead to the development of more effective therapeutics for liver diseases, microphysiological systems, and scalable cell-based therapies.

Data Availability

Data sharing is not applicable to this article as no new data was created or analyzed in this study.




Publication History

Article published online:
04 February 2022

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