Abstract
Effective, targeted therapy for chronic liver disease nonalcoholic steatohepatitis (NASH) is imminent. MicroRNAs (miRNAs) are a potential therapeutic target, and natural products that regulate miRNA expression may be a safe and effective treatment strategy for liver disease. Here, we investigated the functional role of miR-451 and the therapeutic effects of genistein in the NASH mouse model. MiR-451 was downregulated in various types of liver inflammation, and subsequent experiments showed that miR-451 regulates liver inflammation via IL1β. Genistein is a phytoestrogen with anti-inflammatory and anti-oxidant effects. Interestingly, we found that the anti-inflammatory effects of genistein were related to miR-451 and was partially antagonized by the miR-451 inhibitor. MiR-451 overexpression or genistein treatment inhibited IL1β expression and inflammation. Taken together, this study shows that miR-451 has a protective effect on hepatic inflammation, and genistein can be used as a natural promoter of miR-451 to ameliorate NASH.
Highlights
The liver is the largest internal organ of mammals and one of the most active in terms of energy metabolism
In searching the GEO (Gene Expression Omnibus) database, we found that miR-451 was downregulated in patients with alcoholic hepatitis (AH), HCV-induced cirrhosis (HVC-CH), alcohol liver disease-induced cirrhosis (ALD-CH), and leptin-deficient obesity mice (Figure 1A,B)
We showed that IL-6 and TNF-α were gradually upregulated in a dose-dependent manner, while miR-451 expression was gradually downregulated both in NCTC1469 cells (Figure 1C,D) and Raw264.7 cells (Figure 1E,F)
Summary
The liver is the largest internal organ of mammals and one of the most active in terms of energy metabolism. It plays a role in deoxidation, glycogen storage, detoxification, and secretory protein synthesis in mammals [1,2]. Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease with a global prevalence of 25% [10,11]. NAFLD/NASH is closely related to factors such as abnormal lipid metabolism, insulin resistance, oxidative stress, and genetic susceptibility [13,14]. Inflammation is a complication of various liver diseases, so relieving inflammation is one of the most important ways to control the development of liver disease [16,17]
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