Cell-to-Cell Communications in Alcohol-Associated Liver Disease

Natalia A Osna; Akiko Eguchi; Ariel E Feldstein; Hidekazu Tsukamoto; Raghubendra S Dagur; Murali Ganesan; Moses New-Aaron; Madan Kumar Arumugam; Srinivas Chava; Marcelle Ribeiro; Gyongyi Szabo; Sebastian Mueller; Shijin Wang; Cheng Chen; Steven A Weinman; Kusum K Kharbanda

doi:10.3389/fphys.2022.831004

Cell-to-Cell Communications in Alcohol-Associated Liver Disease

Front Physiol. 2022 Feb 21:13:831004. doi: 10.3389/fphys.2022.831004. eCollection 2022.

Authors

Natalia A Osna^{1

2}, Akiko Eguchi³, Ariel E Feldstein⁴, Hidekazu Tsukamoto^{5

6}, Raghubendra S Dagur^{1

2}, Murali Ganesan^{1

2}, Moses New-Aaron^{1

7}, Madan Kumar Arumugam^{1

2}, Srinivas Chava^{1

2}, Marcelle Ribeiro⁸, Gyongyi Szabo⁸, Sebastian Mueller⁹, Shijin Wang⁹, Cheng Chen⁹, Steven A Weinman¹⁰, Kusum K Kharbanda^{1

2

11}

Affiliations

¹ Research Service, Veterans Affairs Nebraska-Western Iowa Health Care System, Omaha, NE, United States.
² Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE, United States.
³ Department of Gastroenterology and Hepatology, Graduate School of Medicine, Mie University, Tsu, Japan.
⁴ Department of Pediatrics, University of California, San Diego, San Diego, CA, United States.
⁵ Southern California Research Center for ALPD and Cirrhosis and Department of Pathology, Keck School of Medicine of the University of Southern California, Los Angeles, CA, United States.
⁶ Greater Los Angeles VA HealthCare System, Los Angeles, CA, United States.
⁷ Department of Environmental Health, Occupational Health, and Toxicology, College of Public Health, University of Nebraska Medical Center, Omaha, NE, United States.
⁸ Harvard Medical School and Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA, United States.
⁹ Salem Medical Center and Center for Alcohol Research, University of Heidelberg, Heidelberg, Germany.
¹⁰ Department of Internal Medicine, University of Kansas Medical Center, Kansas City, KS, United States.
¹¹ Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, United States.

Abstract

This review covers some important new aspects of the alcohol-induced communications between liver parenchymal and non-parenchymal cells leading to liver injury development. The information exchange between various cell types may promote end-stage liver disease progression and involves multiple mechanisms, such as direct cell-to-cell interactions, extracellular vesicles (EVs) or chemokines, cytokines, and growth factors contained in extracellular fluids/cell culture supernatants. Here, we highlighted the role of EVs derived from alcohol-exposed hepatocytes (HCs) in activation of non-parenchymal cells, liver macrophages (LM), and hepatic stellate cells (HSC). The review also concentrates on EV-mediated crosstalk between liver parenchymal and non-parenchymal cells in the settings of HIV- and alcohol co-exposure. In addition, we overviewed the literature on the crosstalk between cell death pathways and inflammasome activation in alcohol-activated HCs and macrophages. Furthermore, we covered highly clinically relevant studies on the role of non-inflammatory factors, sinusoidal pressure (SP), and hepatic arterialization in alcohol-induced hepatic fibrogenesis. We strongly believe that the review will disclose major mechanisms of cell-to-cell communications pertained to alcohol-induced liver injury progression and will identify therapeutically important targets, which can be used for alcohol-associated liver disease (ALD) prevention.

Keywords: HIV; alcohol hepatitis; extracellular vesicles; fibrosis; liver stiffness; pyroptosis.

Abstract

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