Clin Exp Med. 2022 Oct 27. doi: 10.1007/s10238-022-00919-9. Online ahead of print.
The vitamin D receptor (VDR) is a nuclear transcription factor that acts as the main transducer in response to vitamin D (VD), regulating about 3% of the gene expression in the human genome. This study investigated the expression of VDR in the liver of patients with chronic hepatitis B virus (HBV) infection and determined its correlation with liver inflammation and fibrosis. We evaluated the effects of HBV infection on the expression of VDR in vivo and in vitro and further investigate the potential mechanism. Subsequently, the associations between hepatic VDR expression with liver inflammation and fibrosis were statistically analyzed. Results showed that hepatic VDR expression was significantly decreased in patients with chronic HBV infection as compared to healthy individuals. Similarly, in vitro experiments further confirmed that HBV infection could inhibit the expression of VDR in hepatocytes. Mechanistically, HBV was able to directly induce the expression of miR-125a which inhibited the mRNA and protein levels of VDR. Statistical analysis showed that hepatic VDR expression was significantly negatively correlated with liver inflammation and fibrosis in patients. We conclude that inhibition of hepatic vitamin D receptor expression by HBV/miR-125a is negatively associated with liver inflammation and fibrosis in patients with chronic HBV infection.