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

Abstract

Non-alcoholic fatty liver disease (NAFLd) is a clini- cally 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 medi- cations, 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 progres- sion 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 chan- nels can be blocked or activated, which exerts anti-steatotic, anti-inflammatory, anti-fibrotic and other effects, which ulti- mately 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.