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Pharmacological research

Pharmacological research

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Antagonising Yin Yang 1 ameliorates the symptoms of lupus nephritis via modulating T lymphocyte signaling

Published:1 December 2024 DOI: 10.1016/j.phrs.2024.107525
Haoxing Yuan, Zheng Peng, Shuwen Liu

Abstract

Lupus nephritis (LN) is a chronic complication of systemic lupus erythematosus (SLE). At present, no drugs are capable of delaying the progression of LN without a risk of serious side effects. There is thus a pressing need for further studies of LN pathogenesis to identify novel therapeutic targets and aid in the development of new approaches to treating this debilitating disease. In this study, a multi-omics approach was used to characterize the pathogenesis of LN and to identify disease-related targets, ultimately leading to the identification and validation of Yin Yang 1 (YY1) as a promising therapeutic target in LN. A rapid approach to efficiently screening for candidate YY1 ligands was implemented using drug databases that established rebamipide as a YY1 antagonist suitable for use in the management of LN. Specifically, the YY1 antagonist activity of rebamipide was found to regulate lymphocyte activity, reduce autoantibody production, limit immune complex deposition, and suppress macrophage activation while improving symptoms in a murine model of LN. Results supportive of a similar pathologic mechanism of action were also obtained when analyzing renal tissue sections from LN patients, underscoring the potential clinical significance of YY1 and its antagonist rebamipide, suggesting that rebamipide may have positive effects on lymphocytes and may improve symptoms in treated patients. This study provides a robust foundation for further research focused on the pathogenesis and treatment of LN.

Substances (6)

Materials
Procduct Name CAS Molecular Formula Supplier Price
Crystal Violet 548-62-9 C25H30ClN3 876 suppliers $5.00-$2290.00
Penicillin G sodium salt 69-57-8 C16H17N2NaO4S 521 suppliers $12.00-$775.16
Rebamipide 90098-04-7 C19H15ClN2O4 494 suppliers $6.00-$1593.90
Streptomycin 57-92-1 C21H39N7O12 160 suppliers Inquiry
HEXADIMETHRINE BROMIDE 28728-55-4 C39H90Br6N6X2 114 suppliers $11.00-$950.00
FETUIN 9014-81-7 NULL 92 suppliers $37.07-$4810.00
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