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Liver sinusoidal endothelial transcription factors in metabolic homeostasis and disease
File(s)
jme-JME-23-0026.pdf (3.45 MB)
Published version
Author(s)
Nagy, Dorka
Maude, Hannah
Birdsey, Graeme M
Randi, Anna M
Cebola, Inês
Type
Journal Article
Abstract
Liver sinusoidal endothelial cells (LSECs) are highly specialized endothelial cells that form the liver microvasculature. LSECs maintain liver homeostasis, scavenging bloodborne molecules, regulating immune response, and actively promoting hepatic stellate cell quiescence. These diverse functions are underpinned by a suite of unique phenotypical attributes distinct from other blood vessels. In recent years, studies have begun to reveal the specific contributions of LSECs to liver metabolic homeostasis and how LSEC dysfunction associates with disease aetiology. This has been particularly evident in the context of non-alcoholic fatty liver disease (NAFLD), the hepatic manifestation of metabolic syndrome, which is associated with loss of key LSEC phenotypical characteristics and molecular identity. Comparative transcriptome studies of LSECs and other endothelial cells, together with rodent knockout models, have revealed that loss of LSEC identity through disruption of core transcription factor activity leads to impaired metabolic homeostasis and to hallmarks of liver disease. This review explores the current knowledge of LSEC transcription factors, covering their roles in LSEC development and maintenance of key phenotypic features, which, when disturbed, lead to loss of liver metabolic homeostasis and promote features of chronic liver diseases, such as non-alcoholic liver disease.
Date Issued
2023-08
Date Acceptance
2023-06-12
Citation
Journal of Molecular Endocrinology, 2023, 71 (2), pp.1-20
URI
URL
DOI
ISSN
0952-5041
Publisher
BioScientifica
Start Page
1
End Page
20
Journal / Book Title
Journal of Molecular Endocrinology
Volume
71
Issue
2
Copyright Statement
© 2023 The authors 2023. This work is published under a CC BY licence.
License URL
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/37306684
PII: JME-23-0026
Publication Status
Published
Coverage Spatial
England
Article Number
e230026
Date Publish Online
2023-07-18