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Hepatic vitamin D receptor expression is negatively associated with liver inflammation and fibrosis in patients with chronic HBV infection

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Abstract

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.

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Data availability

The datasets generated and/or analyzed during the current study are not publicly available due to privacy restrictions but are available from the corresponding author on reasonable request.

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Funding

This work was supported by Anhui Provincial Natural Science Foundation (2108085MH301).

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Authors and Affiliations

  1. Department of Medical Technology, Anhui Medical College, Hefei, 230601, Anhui, China

    Kai Yang & Ying Pan

  2. Department of Clinical Laboratory, The Second Hospital of Anhui Medical University, Hefei, 230601, Anhui, China

    Hao Zhang

  3. Department of Infectious Disease, The Second Hospital of Anhui Medical University, Hefei, 230601, Anhui, China

    Lei Jin

  4. Department of Pathology, The Second Hospital of Anhui Medical University, Hefei, 230601, Anhui, China

    Xian Wang

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  1. Kai Yang
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  2. Ying Pan
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  3. Hao Zhang
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  4. Lei Jin
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  5. Xian Wang
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Contributions

KY designed the experiment. KY, YP and HZ performed the main experiment. LJ collected clinical data and biospecimen. XW carried out the immunoassays and immunohistochemical evaluation. KY and YP wrote the paper. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Kai Yang.

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The authors declare that they have no conflict of interest.

Ethical standards

This study was approved by the Ethics Board of Anhui Medical College and the Second Hospital of Anhui Medical University, and informed consent was obtained from all participating study subjects.

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Yang, K., Pan, Y., Zhang, H. et al. Hepatic vitamin D receptor expression is negatively associated with liver inflammation and fibrosis in patients with chronic HBV infection. Clin Exp Med 23, 2151–2158 (2023). https://doi.org/10.1007/s10238-022-00919-9

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  • DOI: https://doi.org/10.1007/s10238-022-00919-9

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