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慢性乙型肝炎病毒感染者肝维生素 D 受体表达与肝炎症和纤维化呈负相关。

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

机构信息

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

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

出版信息

Clin Exp Med. 2023 Oct;23(6):2151-2158. doi: 10.1007/s10238-022-00919-9. Epub 2022 Oct 27.

DOI:10.1007/s10238-022-00919-9
PMID:36289101
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.

摘要

维生素 D 受体(VDR)是一种核转录因子,作为对维生素 D(VD)的主要转导物,调节人类基因组中约 3%的基因表达。本研究调查了慢性乙型肝炎病毒(HBV)感染患者肝脏中 VDR 的表达,并确定其与肝炎症和纤维化的相关性。我们评估了 HBV 感染对体内和体外 VDR 表达的影响,并进一步研究了潜在的机制。随后,对肝 VDR 表达与肝炎症和纤维化之间的关联进行了统计学分析。结果表明,与健康个体相比,慢性 HBV 感染患者的肝 VDR 表达显著降低。同样,体外实验进一步证实 HBV 感染可以抑制肝细胞中 VDR 的表达。机制上,HBV 能够直接诱导 miR-125a 的表达,从而抑制 VDR 的 mRNA 和蛋白水平。统计学分析表明,肝 VDR 表达与慢性 HBV 感染患者的肝炎症和纤维化呈显著负相关。我们得出结论,HBV/miR-125a 抑制肝维生素 D 受体表达与慢性 HBV 感染患者的肝炎症和纤维化呈负相关。

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本文引用的文献

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The Effects of Vitamin D Supplementation on Anthropometric and Biochemical Indices in Patients With Non-alcoholic Fatty Liver Disease: A Systematic Review and Meta-analysis.维生素D补充剂对非酒精性脂肪性肝病患者人体测量学和生化指标的影响:一项系统评价和荟萃分析
Front Pharmacol. 2021 Nov 3;12:732496. doi: 10.3389/fphar.2021.732496. eCollection 2021.
2
Vitamin D signaling inhibits HBV activity by directly targeting the HBV core promoter.维生素 D 信号通过直接靶向 HBV 核心启动子抑制 HBV 活性。
J Biol Chem. 2021 Oct;297(4):101233. doi: 10.1016/j.jbc.2021.101233. Epub 2021 Sep 23.
3
MiR-125b promotes migration and invasion by targeting the vitamin D receptor in renal cell carcinoma.
miR-125b 通过靶向维生素 D 受体促进肾细胞癌的迁移和侵袭。
Int J Med Sci. 2021 Jan 1;18(1):150-156. doi: 10.7150/ijms.49328. eCollection 2021.
4
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Life Sci. 2021 Jan 1;264:118666. doi: 10.1016/j.lfs.2020.118666. Epub 2020 Oct 29.
5
Importance of miR-125a-5p and miR-122-5p expression in patients with HBV infection.miR-125a-5p 和 miR-122-5p 表达在乙型肝炎病毒感染患者中的重要性。
Cell Mol Biol (Noisy-le-grand). 2020 Jul 31;66(5):1-8.
6
Serum Vitamin D Levels in Chronic Hepatitis B Patients Before and During Treatment.慢性乙型肝炎患者治疗前后血清维生素 D 水平。
Infect Disord Drug Targets. 2020;20(6):840-847. doi: 10.2174/1871526519666191112112903.
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