Publication Date
6-28-2024
Journal
Journal of Molecular Medicine
Abstract
The rapidly aging population is consuming more alcohol, leading to increased alcohol-associated acute pancreatitis (AAP) with high mortality. However, the mechanisms remain undefined, and currently there are no effective therapies available. This study aims to elucidate aging- and alcohol-associated spatial transcriptomic signature by establishing an aging AAP mouse model and applying Visium spatial transcriptomics for understanding of the mechanisms in the context of the pancreatic tissue. Upon alcohol diet feeding and caerulein treatment, aging mice (18 months) developed significantly more severe AAP with 5.0-fold increase of injury score and 2.4-fold increase of amylase compared to young mice (3 months). Via Visium spatial transcriptomics, eight distinct tissue clusters were revealed from aggregated transcriptomes of aging and young AAP mice: five acinar, two stromal, and one islet, which were then merged into three clusters: acinar, stromal, and islet for the comparative analysis. Compared to young AAP mice, > 1300 differentially expressed genes (DEGs) and approximately 3000 differentially regulated pathways were identified in aging AAP mice. The top five DEGs upregulated in aging AAP mice include Mmp8, Ppbp, Serpina3m, Cxcl13, and Hamp with heterogeneous distributions among the clusters. Taken together, this study demonstrates spatial heterogeneity of inflammatory processes in aging AAP mice, offering novel insights into the mechanisms and potential drivers for AAP development.
Keywords
Animals, Aging, Transcriptome, Mice, Pancreatitis, Gene Expression Profiling, Disease Models, Animal, Male, Inflammation, Mice, Inbred C57BL, Ethanol, Pancreatitis, Alcoholic, Acute Disease, Pancreas
Included in
Biological Phenomena, Cell Phenomena, and Immunity Commons, Internal Medicine Commons, Medical Molecular Biology Commons, Mental and Social Health Commons, Pathological Conditions, Signs and Symptoms Commons, Surgery Commons
Comments
Supplementary Materials
PMID: 38940937