Hepatic ZBTB22-mediated detoxification ameliorates acetaminophen-induced liver injury by inhibiting pregnane X receptor signaling
Yingjian Chen,
Tianqi Cui,
Shaorong Xiao,
Tianyao Li,
Yadi Zhong,
Kaijia Tang,
Jingyi Guo,
Shangyi Huang,
Jiabing Chen,
Jiayu Li,
Qi Wang,
Jiawen Huang,
Huafeng Pan,
Yong Gao
Affiliations
Yingjian Chen
Science and Technology Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou 510080, China
Tianqi Cui
Science and Technology Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou 510080, China
Shaorong Xiao
School of Basic Medical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 510080, China
Tianyao Li
Science and Technology Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou 510080, China
Yadi Zhong
Science and Technology Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou 510080, China
Kaijia Tang
Science and Technology Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou 510080, China
Jingyi Guo
Science and Technology Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou 510080, China
Shangyi Huang
Science and Technology Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou 510080, China
Jiabing Chen
Science and Technology Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou 510080, China
Jiayu Li
Science and Technology Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou 510080, China
Qi Wang
Science and Technology Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou 510080, China; Corresponding author
Jiawen Huang
Science and Technology Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou 510080, China; Corresponding author
Huafeng Pan
Science and Technology Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou 510080, China; Corresponding author
Yong Gao
Science and Technology Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou 510080, China; Jiangsu Collaborative Innovation Center of Traditional Chinese Medicine in Prevention and Treatment of Tumor, Nanjing University of Chinese Medicine, Nanjing 210023, China; Corresponding author
Summary: Overdose acetaminophen (APAP) can cause acute liver injury (ALI), but the underlying mechanism remains undetermined. This study explored the role of hepatic Zinc Finger And BTB Domain Containing 22 (ZBTB22) in defense against APAP-mediated hepatotoxicity. The results showed that hepatic ZBTB22 expression was significantly reduced in patients with ALI and mice. In mouse primary hepatocytes (MPHs), ZBTB22 deletion aggravated APAP overdose-induced ALI, whereas ZBTB22 overexpression attenuated that pathological progression. The results were further verified in ZBTB22 over-express or knockout mice models. In parallel, hepatocyte-specific ZBTB22 knockout also enhanced ALI. Furthermore, ZBTB22 decreased pregnane X receptor (PXR) expression, and the PXR activator pregnane-16α-carbonitrile suppressed the protective effect of ZBTB22 in APAP-induced ZBTB22-overexpressing mice. Collectively, our findings highlight the protective effect of ZBTB22 against APAP-induced ALI and unravel PXR signaling as the potential mechanism. Strategies to increase hepatic ZBTB22 expression represent a promising therapeutic approach for APAP overdose-induced ALI.
