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Neutrophils in MASLD and MASH
Sanjeeb Shrestha 1 (Visiting Professor), Jae-Han Jeon 2 (Assistant Professor), Chang-Won Hong 3,* (Associate Professor)
1Department of Physiology, Kyungpook National University,
2Department of Internal Medicine, Kyungpook National University Chilgok Hospital,
3Research Institute of Aging and Metabolism, Kyungpook National University
Abstract
Metabolic Dysfunction Associated Steatotic Liver Disease (MASLD) and its progressive form, Metabolic Dysfunction Associated Steatohepatitis (MASH), represent significant health concerns associated with the metabolic syndrome. These conditions are characterized by excessive hepatic fat accumulation, inflammation, and potential progression to cirrhosis and hepatocellular carcinoma. Neutrophils, as innate immune cells, play a pivotal role in the development of MASLD and MASH. They infiltrate the hepatic microenvironment in response to inflammatory cytokines and damage associated molecular patterns (DAMPs) derived from liver, and exacerbate tissue damage through the release of reactive oxygen species (ROS), cytokines, and neutrophil extracellular traps (NETs). Moreover, neutrophils disrupt the metabolism of hepatocytes through key factors such as neutrophil elastase (NE) and human neutrophil peptides-1 (HNP-1), leading to inflammation and fibrosis, while myeloperoxidase (MPO) and lipocalin (LCN2) are involved in the inflammatory and fibrotic processes. In contrast, neutrophils contribute to liver protection and repair through mechanisms involving microRNA-223 and matrix metalloproteinase 9 (MMP9). This dual role of neutrophils highlights their significance in the pathogenesis of MASLD and MASH. This review summarizes the current understanding from recent studies on the involvement of neutrophils and MASLD and MASH. Understanding the complex roles of neutrophils within the liver's unique microenvironment offers insights into novel therapeutic strategies, emphasizing the need for further research to explore neutrophil-targeted interventions in managing MASLD and MASH.
Abstract, Accepted Manuscript [Submitted on April 16, 2024, Accepted on June 11, 2024]
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