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The role of retinoic acid receptor signaling in liver cells during Alcohol-associated liver disease resolution by spatial transcriptomics analysis

ABSTRACT: Abstinence is beneficial for patients with alcohol-associated liver disease (ALD), but disease resolution after alcohol cessation occurs slowly and only in a subset of patients. Mechanisms of fibrosis resolution in ALD are not yet fully understood. Previous work highlights the importance of liver niche remodeling around areas of fibrosis that involves protein and metabolite mediated cell-cell crosstalk between hepatocytes and non-parenchymal cells. We aimed to study the mechanisms of ALD resolution using spatial transcriptomics. We found that retinoic acid metabolism strongly associated with improved fibrosis resolution in a mouse model of ALD. In agreement with this finding, mice treated with RAR agonist AM580 after alcohol cessation showed improved fibrosis resolution. Spatial transcriptomics analysis of agonist treated mice and controls suggested that RAR activation dramatically altered liver niches thus promoting pro-resolving changes in liver cells.

ORGANISM(S): Mus musculus

PROVIDER: GSE320403 | GEO | 2026/03/23

REPOSITORIES: GEO

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