Role of Ca<sup>2+</sup> channels in non-alcoholic fatty liver disease and their implications for therapeutic strategies (Review)

Chen,Xingyue; Zhang,Li; Zheng,Liming; Tuo,Biguang

doi:10.3892/ijmm.2022.5169

Role of Ca²⁺ channels in non-alcoholic fatty liver disease and their implications for therapeutic strategies (Review)

Authors:
- Xingyue Chen
- Li Zhang
- Liming Zheng
- Biguang Tuo
View Affiliations

Affiliations: Department of Gastroenterology, Digestive Disease Hospital, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou 563003, P.R. China
Published online on: July 4, 2022 https://doi.org/10.3892/ijmm.2022.5169
Article Number: 113
Copyright: © Chen et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Non‑alcoholic fatty liver disease (NAFLD) is a clinically progressive illness that can advance from simple fatty liver to non-alcoholic hepatitis and liver fibrosis. Cirrhosis and hepatocellular carcinoma are two of the most common diseases caused by NAFLD. As there are no early disease biomarkers and no US Food and Drug Administration‑approved medications, treatment for NAFLD is still focused on altering lifestyle and dietary habits, which makes it difficult to treat effectively. As a result, a novel treatment is urgently needed to prevent NAFLD progression. Calcium (Ca²⁺) channels regulate intracellular Ca²⁺ homeostasis via the mediation of Ca²⁺ flow. Previous studies have reported that Ca²⁺ channel expression varies throughout the development and progression of NAFLD, which results in the dysregulation of intracellular Ca²⁺ homeostasis, endoplasmic reticulum stress, mitochondrial dysfunction and autophagy suppression, all of which contribute to NAFLD progression. Several types of Ca²⁺ channels (including two‑pore segment channel 2, transient receptor potential, inositol triphosphate receptor, voltage‑dependent anion channel 1, store‑operated Ca²⁺ entry, purinergic receptor X7 and potassium Ca²⁺‑activated channel subfamily N member 4) have been identified as potential targets for preventing NAFLD development and controlling intracellular Ca²⁺ homeostasis. To achieve this, these channels can be blocked or activated, which exerts anti‑steatotic, anti‑inflammatory, anti‑fibrotic and other effects, which ultimately prevents the development of NAFLD. In the present review NAFLD therapeutics and the treatments that target Ca²⁺ channels that are currently being developed were examined.

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