-Original-

Vitamin D Receptor Regulates Autophagy to Inhibit Apoptosis and Promote Proliferation in Hepatocyte Injury

Mingming Fang^1,2 and Chen Zhong^3,4

¹Department of Neurology, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Jiangsu Province, China
²Department of Neurology, Jiangsu Province Academy of Traditional Chinese Medicine, Jiangsu Province, China
³Hepatobiliary Center, the First Affiliated Hospital of Nanjing Medical University, Jiangsu Province, China
⁴Key Laboratory of Liver Transplantation, Chinese Academy of Medical Sciences, Jiangsu Province, China

Background: Oxidative stress is an important mechanism in liver ischemia/reperfusion (I/R) injury. Hepatocyte apoptosis and proliferation occur in parallel with liver I/R injury, and the degree of apoptosis and proliferation determines the effects on hepatocytes. Vitamin D receptor (VDR) can lessen liver I/R injury, but previous studies focused mostly on inflammation and immunity.
Methods: H₂O₂ was used to induce hepatocyte injury. Before treatment with H₂O₂, Hep-3B cells were pretreated with paricalcitol (PC) and siRNA-VDR. Rapamycin and chloroquine were also applied in the study.
Results: The number of apoptotic cells was measured with an annexin V (AV)-fluorescein isothiocyanate apoptosis detection kit. Expression of proteins was measured by western blotting. As compared with the H₂O₂+Hep-3B group, levels of AV/PI, cleaved caspase-3, and p62 were lower, and expression levels of Bcl-2, proliferating cell nuclear antigen, and VDR were higher, in the PC+H₂O₂+Hep-3B group. When the VDR gene was silenced by siRNA-VDR in the siRNA-VDR+H₂O₂+Hep-3B group, expressions of AV/PI, cleaved caspase-3, and p62 were upregulated, and expressions of Bcl-2, proliferating cell nuclear antigen, and VDR were downregulated, as compared with values for the siRNA-NC+H₂O₂+Hep-3B group. Treatment with rapamycin or chloroquine partially reversed the effect of PC and siRNA-VDR on apoptosis and proliferation.
Conclusions: VDR mediates hepatocyte apoptosis and proliferation through autophagy.

J Nippon Med Sch 2023; 90: 89-95

Keywords
vitamin D receptor, apoptosis, proliferation, autophagy, hepatocyte injury

Correspondence to
Chen Zhong, Hepatobiliary Center, the First Affiliated Hospital of Nanjing Medical University, NO. 300 Guangzhou Road, Nanjing, Jiangsu Province 210000, China
zc_seaman@126.com

Received, July 22, 2022
Accepted, September 28, 2022