Abstract
The liver accounts for the largest proportion of macrophages in all solid organs of the human body. Liver macrophages are mainly composed of cytolytic cells inherent in the liver and mononuclear macrophages recruited from the blood. Monocytes recruitment occurs mainly in the context of liver injury and inflammation and can be recruited into the liver and achieve a KC-like phenotype. During the immune response of the liver, macrophages/KC cells release inflammatory cytokines and infiltrate into the liver, which are considered to be the common mechanism of various liver diseases in the early stage. Meanwhile, macrophages/KC cells form an interaction network with other liver cells, which can affect the occurrence and progression of liver diseases. From the perspective of liver disease treatment, knowing the full spectrum of macrophage activation, the underlying molecular mechanisms, and their implication in either promoting liver disease progression or repairing injured liver tissue is highly relevant from a therapeutic point of view. Kv1.3 is a subtype of the voltage-dependent potassium channel, whose function is closely related to the regulation of immune cell function. At present, there are few studies on the relationship between Kv1.3 and liver diseases, and the application of its blockers as a potential treatment for liver diseases has not been reported. This manuscript reviewed the physiological characteristics of Kv1.3, the relationship between Kv1.3 and cell proliferation and apoptosis, and the role of Kv1.3 in a variety of liver diseases, so as to provide new ideas and strategies for the prevention and treatment of liver diseases. In short, by understanding the role of Kv1.3 in regulating the functions of immune cells such as macrophages, selective blockers of Kv1.3 or compounds with similar functions can be applied to alleviate the progression of liver diseases and provide new ideas for the prevention and treatment of liver diseases.
Highlights
Liver diseases, including hepatitis B virus (HBV) and hepatitis C virus (HCV) infection, alcoholic liver disease (ALD), non-alcoholic fatty liver disease (NAFLD) and related cirrhosis, liver failure (LF), and hepatocellular carcinoma (HCC), are the main causes of disease and death in the world
In China, viral hepatitis, non-alcoholic fatty liver disease (NAFLD), and alcoholic liver disease (ALD) affect about 300 million people, 130 million of whom are affected by ALD and NAFLD, accounting for half of the population with ALD and NAFLD in the world
Kupffer cells (KCs) are key immune cells in the innate immune system of the liver and play a key role in lipopolysaccharide (LPS)-induced responses, which promote the secretion of inflammatory cytokines, including interleukin-1 (IL1), interleukin-6 (IL-6), monocyte chemical attractant protein 1 (MCP-1), and tumor necrosis factor-α (TNF-α)
Summary
Liver diseases, including hepatitis B virus (HBV) and hepatitis C virus (HCV) infection, alcoholic liver disease (ALD), non-alcoholic fatty liver disease (NAFLD) and related cirrhosis, liver failure (LF), and hepatocellular carcinoma (HCC), are the main causes of disease and death in the world. When the membrane potential is hyperpolarized in T lymphocytes, which causes K+ to flow from the cell to the extracellular, it provides the driving force for Ca2+ to flow into the cell and further promotes the activation of Ca2+-dependent transcription factors, leading to cell proliferation.
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