Review on Biological Characteristics of Kv1.3 and Its Role in Liver Diseases

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.

Potassium channels as novel molecular targets in hepatocellular carcinoma (Review)

“…K + channels fulfill an important role in acute and chronic hepatocyte injury. For instance, margatoxin (MgTX), a Kv1.3-specific blocker, has been shown to reduce the serum levels of TNF-α, IL-6, alanine transaminase and aspartate transaminase to reduce the expression ratio of C-C motif chemokine receptor 2/glutathione reductase 1 double-positive cells and ionized calcium binding adaptor molecule 1/c-type lectin domain family 4 member F positive cells in peripheral mononuclear macrophages, as well as reducing the infiltration rate of peripheral mononuclear macrophages into the liver (32). MgTX has also been shown to markedly protect the liver from acute liver injury.…”

“…In addition, it is a novel target for the prevention and treatment of alcoholic fatty liver disease, precisely since it is able to regulate the function of macrophages. Further studies have indicated that the Kv1.3 pathway may alleviate the development of liver fibrosis by reducing the expression of TGF-β (32). It has been reported that KCa3.1 expression is increased in hepatocytes with liver fibrosis and that these increases coincide with the progression of liver injury.…”

“…Kv1.3, an important regulatory protein of the immune response, has been found in lymphocytes and is mainly involved in immune regulation of the body's immune system (75). Kv1.3 protein on cell membranes is involved in cell proliferation, whereas Kv1.3 channels located on mitochondria are involved in cell apoptosis, and therefore, Kv1.3 located on mitochondria is considered to be a novel tumor biomarker (32,76). It has been reported that the Kv1.3 channel is involved in the proliferation and apoptosis of a variety of different types of tumor.…”

Voltage-Gated Potassium Channels Kv1.3 in Health and Disease

“…A key event in the development of liver fibrosis is an infiltration of a large number of monocyte-derived macrophages into the liver [28]. It was shown that inhibition of Kv1.3 channels expressed in macrophages by the specific inhibitor, margatoxin (MgTX), could reduce serum levels of pro-inflammatory cytokines, such as tumour necrosis factor alpha (TNF-α) or Interleukin 6 (IL-6), and reduce the infiltration of peripheral mononuclear macrophages into the liver, which could significantly protect the liver from the ALI [28]. Activity of Kv1.3 channels is essential for mononuclear cell migration; therefore, inhibition of Kv1.3 channels may reduce macrophage migration.…”

CdTe@CdS quantum dots for labeling and imaging macrophages in liver frozen sections below the freezing point

“…Moreover, they can also induce T cell proliferation and regulate the body's immune response in liver diseases, play a leading role in the defense system, and maintain environmental homeostasis in the normal body. [2][3][4] Therefore, studying the distribution of liver macrophages in the liver can provide important support to further understand the relationship between the liver structure and functions and pathological changes. 5 Locating macrophages in liver tissue with antibodies as probes is a strongly specific and highly sensitive cell labeling technique.…”