Inhibition of TWEAK/Tnfrsf12a axis protects against acute liver failure by suppressing RIPK1-dependent apoptosis

doi:10.1038/s41420-022-01123-0

	Inhibition of TWEAK/Tnfrsf12a axis protects against acute liver failure by suppressing RIPK1-dependent apoptosis
	Li, Zhijie1,2,3 ; Wang, Heming 4; Zhu, Junjin1 ; Nan, Ning1,2,3 ; Lin, Yi1 ; Zhuang, Xuran1 ; Li, Ling1 ; Zhang, Yamin 5; Huang, Pengyu 6
	2022-07-19
发表期刊	CELL DEATH DISCOVERY (IF:6.1[JCR-2023],6.0[5-Year])
EISSN	2058-7716
卷号	8 期号:1
发表状态	已发表
DOI	10.1038/s41420-022-01123-0
摘要	Acute liver failure (ALF) is a severe clinical syndrome characterized by massive death of hepatocytes in a short time, resulting in coagulopathy and hepatic encephalopathy, with a high mortality in patients without pre-existing liver disease. Effective treatment of ALF is currently limited to liver transplantation, highlighting the need for new target therapies. Here, we found that expression of hepatic tumor necrosis factor-like weak inducer of apoptosis (TWEAK) and its receptor tumor necrosis factor receptor superfamily member 12A (Tnfrsf12a) were significantly increased during ALF induced by thioacetamide (TAA) or acetaminophen (APAP). Inhibition of TWEAK/Tnfrsf12a axis markedly attenuated TAA or APAP-induced ALF. Moreover, our results demonstrated that TWEAK/Tnfrsf12a axis induced receptor-interacting protein kinase 1 (RIPK1)-dependent apoptosis of hepatocytes, instead of necroptosis or pyroptosis. Notably, hepatic TNFRSF12A and TWEAK levels were also significantly increased in liver biopsies from ALF patients. In summary, our results demonstrate that during ALF, TWEAK/Tnfrsf12a axis activates RIPK1 in hepatocytes, leading to RIPK1-dependent apoptosis and subsequent liver injury. Therefore, inhibition of either TWEAK/Tnfrsf12a axis or RIPK1-dependent apoptosis attenuates liver injury, providing a new potential therapeutic target for the treatment of ALF.
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收录类别	SCIE
语种	英语
Scopus 记录号	2-s2.0-85134362054
来源库	Scopus
引用统计	正在获取...
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/214811
专题	生命科学与技术学院_博士生生命科学与技术学院_硕士生生命科学与技术学院_PI研究组_向阳飞组
通讯作者	Zhang, Yamin; Huang, Pengyu
作者单位	1.School of Life Science and Technology,ShanghaiTech University,Shanghai,201210,China 2.University of Chinese Academy of Sciences,Beijing,100049,China 3.CAS Center for Excellence in Molecular Cell Science,Chinese Academy of Sciences,Shanghai,200031,China 4.Department of Gastroenterology and Hepatology,Zhongshan Hospital,Fudan University,Shanghai,200032,China 5.Tianjin First Central Hospital,Tianjin,300190,China 6.Institute of Biomedical Engineering,Chinese Academy of Medical Sciences and Peking Union Medical College,Tianjin,300192,China
第一作者单位	生命科学与技术学院
第一作者的第一单位	生命科学与技术学院
推荐引用方式 GB/T 7714	Li, Zhijie,Wang, Heming,Zhu, Junjin,et al. Inhibition of TWEAK/Tnfrsf12a axis protects against acute liver failure by suppressing RIPK1-dependent apoptosis[J]. CELL DEATH DISCOVERY,2022,8(1).
APA	Li, Zhijie.,Wang, Heming.,Zhu, Junjin.,Nan, Ning.,Lin, Yi.,...&Huang, Pengyu.(2022).Inhibition of TWEAK/Tnfrsf12a axis protects against acute liver failure by suppressing RIPK1-dependent apoptosis.CELL DEATH DISCOVERY,8(1).
MLA	Li, Zhijie,et al."Inhibition of TWEAK/Tnfrsf12a axis protects against acute liver failure by suppressing RIPK1-dependent apoptosis".CELL DEATH DISCOVERY 8.1(2022).