Artemisinin analogue SM934 protects against lupus-associated antiphospholipid syndrome via activation of Nrf2 and its targets

doi:10.1007/s11427-020-1840-1

	Artemisinin analogue SM934 protects against lupus-associated antiphospholipid syndrome via activation of Nrf2 and its targets
	Lin, Zemin 2; Liu, Yuting 1,2; Chen, Li 1,2; Cao, Shiqi 1,2; Huang, Yueteng 3; Yang, Xiaoqian 2; Zhu, Fenghua 2; Tang, Wei 1,2; He, Shijun 1,2; Zuo, Jianping 1,2,3
刊名	SCIENCE CHINA-LIFE SCIENCES
	2021-01-19
页码	18
关键词	artemisinin analog antiphospholipid syndrome antiphospholipid syndrome nephropathy associated lupus nephritis oxidative stress inflammation Nrf2
ISSN号	1674-7305
DOI	10.1007/s11427-020-1840-1
通讯作者	He, Shijun(heshijun@simm.ac.cn) ; Zuo, Jianping(jpzuo@simm.ac.cn)
英文摘要	Kidney is a major target organ in both antiphospholipid syndrome (APS) and systemic lupus erythematosus (SLE). The etiology of antiphospholipid syndrome nephropathy associated lupus nephritis (APSN-LN) is intricate and remains largely unrevealed. We proposed in present work, that generation of antiphospholipid antibodies (aPLs), especially those directed towards the oxidized neoepitopes, are largely linked with the redox status along with disease progression. Moreover, we observed that compromised antioxidative capacity coincided with turbulence of inflammatory cytokine profile in the kidney of male NZWxBXSB F1 mice suffered from APSN-LN. SM934 is an artemisinin derivative that has been proved to have potent immunosuppressive properties. In current study, we elaborated the therapeutic benefits of SM934 in male NZWxBXSB F1 mice, a murine model develops syndrome resembled human APS associated with SLE, for the first time. SM934 treatment comprehensively impeded autoantibodies production, inflammatory cytokine accumulation and excessive oxidative stress in kidney. Among others, we interpreted in present work that both anti-inflammatory and antioxidative effects of SM934 is closely correlated with the enhancement of Nrf2 signaling and expression of its targets. Collectively, our finding confirmed that therapeutic strategy simultaneously exerting antioxidant and anti-inflammatory efficacy provide a novel feasible remedy for treating APSN-LN.
资助项目	National Natural Science Foundation of China[81903882] ; National Natural Science Foundation of China[81871240] ; National Science and Technology Major Project New Drug Creation and Manufacturing Program[2018ZX09711002-014-001] ; Personalized Medicines-Molecular Signature-based Drug Discovery and Development ; Strategic Priority Research Program of the Chinese Academy of Sciences[XDA12020107] ; Strategic Priority Research Program of the Chinese Academy of Sciences[XDA12020369]
WOS关键词	OXIDATIVE STRESS ; RENAL INVOLVEMENT ; INFLAMMATION ; CELLS ; ERYTHEMATOSUS ; PATHOGENESIS ; BIOMARKERS ; ANTIBODIES ; PATHWAY ; DISEASE
WOS研究方向	Life Sciences & Biomedicine - Other Topics
语种	英语
出版者	SCIENCE PRESS
WOS记录号	WOS:000611062500001
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/295989]
专题	中国科学院上海药物研究所
通讯作者	He, Shijun; Zuo, Jianping
作者单位	1.Univ Chinese Acad Sci, Beijing 100049, Peoples R China 2.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Lab Immunopharmacol, Shanghai 201203, Peoples R China 3.Shanghai Univ Tradit Chinese Med, Lab Immunol & Virol, Shanghai 201203, Peoples R China
推荐引用方式 GB/T 7714	Lin, Zemin,Liu, Yuting,Chen, Li,et al. Artemisinin analogue SM934 protects against lupus-associated antiphospholipid syndrome via activation of Nrf2 and its targets[J]. SCIENCE CHINA-LIFE SCIENCES,2021:18.
APA	Lin, Zemin.,Liu, Yuting.,Chen, Li.,Cao, Shiqi.,Huang, Yueteng.,...&Zuo, Jianping.(2021).Artemisinin analogue SM934 protects against lupus-associated antiphospholipid syndrome via activation of Nrf2 and its targets.SCIENCE CHINA-LIFE SCIENCES,18.
MLA	Lin, Zemin,et al."Artemisinin analogue SM934 protects against lupus-associated antiphospholipid syndrome via activation of Nrf2 and its targets".SCIENCE CHINA-LIFE SCIENCES (2021):18.