In:
Hepatology, Ovid Technologies (Wolters Kluwer Health)
Abstract:
Nonalcoholic steatohepatitis (NASH) represents a severe stage of fatty liver disease characterized by hepatocyte injury, inflammation, and liver fibrosis. Myeloid-derived innate immune cells, such as macrophages and dendritic cells, play an important role in host defense and disease pathogenesis. Despite this, the nature of transcriptomic reprogramming of myeloid cells in NASH liver and its contribution to disease progression remain incompletely defined. In this study, we performed bulk and single-cell RNA sequencing analysis to delineate the landscape of macrophage and dendritic cell transcriptomes in healthy and NASH liver. Our analysis uncovered cell type-specific patterns of transcriptomic reprogramming upon diet-induced NASH. We identified Brain abundant membrane attached signal protein 1 (Basp1) as a myeloid-enriched gene that is markedly induced in mouse and human NASH liver. Myeloid-specific inactivation of Basp1 attenuates the severity of diet-induced NASH pathologies as shown by reduced hepatocyte injury and liver fibrosis in mice. Mechanistically, cultured macrophages lacking Basp1 exhibited diminished response to pro-inflammatory stimuli, impaired NLRP3 inflammasome activation, and reduced cytokine secretion. Together, these findings uncover Basp1 as a critical regulator of myeloid inflammatory signaling that underlies NASH pathogenesis.
Type of Medium:
Online Resource
ISSN:
0270-9139
DOI:
10.1097/HEP.0000000000000537
Language:
English
Publisher:
Ovid Technologies (Wolters Kluwer Health)
Publication Date:
2023
detail.hit.zdb_id:
1472120-X
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