Restricted immunological and cellular pathways are shared by murine models of chronic alcohol consumption

Alyx Vogle, Tongqi Qian, Shijia Zhu, Elizabeth Burnett, Holger Fey, Zhibin Zhu, Ali Keshavarzian, Maliha Shaikh, Yujin Hoshida, Miran Kim, Costica Aloman

Research output: Contribution to journalArticle

Abstract

Murine models of chronic alcohol consumption are frequently used to investigate alcoholic liver injury and define new therapeutic targets. Lieber-DeCarli diet (LD) and Meadows-Cook diet (MC) are the most accepted models of chronic alcohol consumption. It is unclear how similar these models are at the cellular, immunologic, and transcriptome levels. We investigated the common and specific pathways of LD and MC models. Livers from LD and MC mice were subjected to histologic changes, hepatic leukocyte population, hepatic transcripts level related to leukocyte recruitment, and hepatic RNA-seq analysis. Cross-species comparison was performed using the alcoholic liver disease (ALD) transcriptomic public dataset. Despite LD mice have increased liver injury and steatosis by alcohol exposure, the number of CD45+ cells were reduced. Opposite, MC mice have an increased number of monocytes/liver by alcohol. The pattern of chemokine gradient, adhesion molecules, and cytokine transcripts is highly specific for each model, not shared with advanced human alcoholic liver disease. Moreover, hepatic RNA-seq revealed a limited and restricted number of shared genes differentially changed by alcohol exposure in these 2 models. Thus, mechanisms involved in alcohol tissue injury are model-dependent at multiple levels and raise the consideration of significant pathophysiological diversity of human alcoholic liver injury.

Original languageEnglish (US)
Article number2451
JournalScientific reports
Volume10
Issue number1
DOIs
StatePublished - Dec 1 2020

ASJC Scopus subject areas

  • General

Fingerprint Dive into the research topics of 'Restricted immunological and cellular pathways are shared by murine models of chronic alcohol consumption'. Together they form a unique fingerprint.

  • Cite this

    Vogle, A., Qian, T., Zhu, S., Burnett, E., Fey, H., Zhu, Z., Keshavarzian, A., Shaikh, M., Hoshida, Y., Kim, M., & Aloman, C. (2020). Restricted immunological and cellular pathways are shared by murine models of chronic alcohol consumption. Scientific reports, 10(1), [2451]. https://doi.org/10.1038/s41598-020-59188-9