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Semin Liver Dis 2023; 43(03): 245-257
DOI: 10.1055/a-2128-5907
Review Article

Angiocrine Signaling in Sinusoidal Health and Disease

Shawna A. Cooper
1   Biochemistry and Molecular Biology Graduate Program, Mayo Clinic Graduate School of Biomedical Sciences, Mayo Clinic, Rochester, Minnesota
,
Enis Kostallari
2   Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
,
Vijay H. Shah
2   Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
› Author Affiliations Funding This paper received funding from the American Association for the Study of Liver Diseases Pinnacle Award, Gilead Scholar award to E.K.; NIDDK-supported 5T32DK124190 to S.A.C.; and P30DK084567 to the Mayo Clinic Center for Cell Signaling in Gastroenterology.
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Abstract

Liver sinusoidal endothelial cells (LSECs) are key players in maintaining hepatic homeostasis. They also play crucial roles during liver injury by communicating with liver cell types as well as immune cells and promoting portal hypertension, fibrosis, and inflammation. Cutting-edge technology, such as single cell and spatial transcriptomics, have revealed the existence of distinct LSEC subpopulations with a clear zonation in the liver. The signals released by LSECs are commonly called “angiocrine signaling.” In this review, we summarize the role of angiocrine signaling in health and disease, including zonation in healthy liver, regeneration, fibrosis, portal hypertension, nonalcoholic fatty liver disease, alcohol-associated liver disease, aging, drug-induced liver injury, and ischemia/reperfusion, as well as potential therapeutic advances. In conclusion, sinusoidal endotheliopathy is recognized in liver disease and promising preclinical studies are paving the path toward LSEC-specific pharmacotherapies.

Keywords

angiocrine signaling - liver sinusoidal endothelial cells - liver health - liver disease - therapeutics


Publication History

Accepted Manuscript online:
13 July 2023

Article published online:
11 August 2023

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