Oxymatrine Ameliorates Lupus Nephritis by Targeting the YY1-Mediated IL-6/STAT3 Axis

被引:0
|
作者
Yuan, Haoxing [1 ]
Peng, Zheng [1 ]
Li, Honglian [1 ]
Rao, Yuzhen [1 ]
Lu, Kunyu [1 ]
Yang, Chan [1 ]
Cheng, Chen [1 ]
Liu, Shuwen [1 ,2 ,3 ]
机构
[1] Southern Med Univ, Sch Pharmaceut Sci, Guangdong Prov Key Lab New Drug Screening, NMPA Key Lab Drug Metab Res & Evaluat, Guangzhou 510515, Peoples R China
[2] Southern Med Univ, Guangdong Prov Inst Nephrol, State Key Lab Organ Failure Res, Guangzhou 510515, Peoples R China
[3] Southern Med Univ, Innovat Ctr Med Basic Res Inflammat & Immune Relat, Minist Educ, Guangzhou 510515, Peoples R China
关键词
lupus nephritis; Yin Yang 1; inflammatory factors; oxymatrine; INJURY; DIHYDROARTEMISININ; FIBROSIS; YY1;
D O I
10.3390/ijms252212260
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Lupus nephritis (LN) is a severe form of systemic lupus erythematosus (SLE), characterized by inflammation in the renal glomeruli and tubules. Previous research has demonstrated that dihydroartemisinin (DHA) can reduce inflammatory damage in LN mouse models. Oxymatrine, which has similar biological properties to DHA, may also provide therapeutic benefits. This study aims to investigate the effects of oxymatrine on LN using a murine model and examines its molecular mechanisms through an analysis of microarray datasets from LN patients. The analysis identified differentially expressed genes (DEGs) in renal tissues, regulated by the transcription factor Yin Yang 1 (YY1), which was found to be significantly upregulated in LN patient kidneys. The results indicate that oxymatrine targets the YY1/IL-6/STAT3 signaling pathway. In cell models simulating renal inflammation, oxymatrine reduced YY1 expression and inhibited the secretion of inflammatory factors (IFs), thereby diminishing inflammation. YY1 is crucial in modulating IFs' secretion and contributing to LN pathogenesis. Additionally, oxymatrine's interaction with YY1, leading to its downregulation, appears to be a key mechanism in alleviating LN symptoms. These findings support oxymatrine as a promising therapeutic agent for LN, offering new avenues for treating this autoimmune kidney disorder.
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页数:16
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