Aging- and alcohol-associated spatial transcriptomic signature in mouse acute pancreatitis reveals heterogeneity of inflammation and potential pathogenic factors.

Autor: Tindall RR; Department of Surgery, UTHealth at Houston, Houston, TX, 77030, USA., Yang Y; McWilliams School of Biomedical Informatics, UTHealth at Houston, Houston, TX, 77030, USA., Hernandez I; Department of Surgery, UTHealth at Houston, Houston, TX, 77030, USA., Qin A; Department of Surgery, UTHealth at Houston, Houston, TX, 77030, USA., Li J; Department of Surgery, UTHealth at Houston, Houston, TX, 77030, USA., Zhang Y; Department of Surgery, UTHealth at Houston, Houston, TX, 77030, USA., Gomez TH; Center for Laboratory Animal Medicine and Care, UTHealth at Houston, Houston, TX, 77030, USA., Younes M; Department of Pathology, George Washington University School of Medicine and Health Sciences, Washington, DC, 20037, USA., Shen Q; Department of Interdisciplinary Oncology, Louisiana State Univ. Health Sciences Center, New Orleans, LA, 70112, USA., Bailey-Lundberg JM; Department of Anesthesiology, Critical Care and Pain Medicine, UTHealth at Houston, Houston, TX, 77030, USA., Zhao Z; Center for Precision Health, McWilliams School of Biomedical Informatics, UTHealth at Houston, Houston, TX, 77030, USA., Kraushaar D; Genomic and RNA Profiling Core, Baylor College of Medicine, Houston, TX, 77030, USA., Castro P; Human Tissue Acquisition & Pathology Core, Baylor College of Medicine, Houston, TX, 77030, USA., Cao Y; Department of Surgery, UTHealth at Houston, Houston, TX, 77030, USA. Yanna.Cao@uth.tmc.edu., Zheng WJ; McWilliams School of Biomedical Informatics, UTHealth at Houston, Houston, TX, 77030, USA. Wenjin.J.Zheng@uth.tmc.edu., Ko TC; Department of Surgery, UTHealth at Houston, Houston, TX, 77030, USA. Tien.C.Ko@uth.tmc.edu.
Jazyk: angličtina
Zdroj: Journal of molecular medicine (Berlin, Germany) [J Mol Med (Berl)] 2024 Aug; Vol. 102 (8), pp. 1051-1061. Date of Electronic Publication: 2024 Jun 28.
DOI: 10.1007/s00109-024-02460-6
Abstrakt: 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. KEY MESSAGES: Mechanisms regarding high mortality of AAP in aging remain undefined. An aging AAP mouse model was developed recapturing clinical exhibition in humans. Spatial transcriptomics identified contrasted DEGs in aging vs. young AAP mice. Top five DEGs were Mmp8, Ppbp, Serpina3m, Cxcl13, and Hamp in aging vs. young AAP mice. Our findings shed insights for identification of molecular drivers in aging AAP.
(© 2024. The Author(s).)
Databáze: MEDLINE
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