Antagonising Yin Yang 1 ameliorates the symptoms of lupus nephritis via modulating T lymphocyte signaling
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...
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| Format: | Article |
| Language: | English |
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Elsevier
2024-12-01
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| Series: | Pharmacological Research |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S1043661824004705 |
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| author | Haoxing Yuan Zheng Peng Meilian Zhang Honglian Li Kunyu Lu Chan Yang Minmin Li Shuwen Liu |
| author_facet | Haoxing Yuan Zheng Peng Meilian Zhang Honglian Li Kunyu Lu Chan Yang Minmin Li Shuwen Liu |
| author_sort | Haoxing Yuan |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-eaf515a33e6c4fe184566b84b8aa9c18 |
| institution | Kabale University |
| issn | 1096-1186 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Pharmacological Research |
| spelling | doaj-art-eaf515a33e6c4fe184566b84b8aa9c182024-12-18T08:47:24ZengElsevierPharmacological Research1096-11862024-12-01210107525Antagonising Yin Yang 1 ameliorates the symptoms of lupus nephritis via modulating T lymphocyte signalingHaoxing Yuan0Zheng Peng1Meilian Zhang2Honglian Li3Kunyu Lu4Chan Yang5Minmin Li6Shuwen Liu7Guangdong Provincial Key Laboratory of New Drug Screening, NMPA Key Laboratory of Drug Metabolism Research and Evaluation, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, ChinaGuangdong Provincial Key Laboratory of New Drug Screening, NMPA Key Laboratory of Drug Metabolism Research and Evaluation, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, ChinaGuangdong Provincial Key Laboratory of New Drug Screening, NMPA Key Laboratory of Drug Metabolism Research and Evaluation, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, ChinaGuangdong Provincial Key Laboratory of New Drug Screening, NMPA Key Laboratory of Drug Metabolism Research and Evaluation, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, ChinaGuangdong Provincial Key Laboratory of New Drug Screening, NMPA Key Laboratory of Drug Metabolism Research and Evaluation, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, ChinaGuangdong Provincial Key Laboratory of New Drug Screening, NMPA Key Laboratory of Drug Metabolism Research and Evaluation, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, ChinaCenter of Clinical Laboratory, The First Affiliated Hospital of Jinan University, Guangzhou 510630, ChinaGuangdong Provincial Key Laboratory of New Drug Screening, NMPA Key Laboratory of Drug Metabolism Research and Evaluation, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China; State Key Laboratory of Organ Failure Research, Guangdong Provincial Institute of Nephrology, Southern Medical University, Guangzhou 510515, China; Innovation Center for Medical Basic Research on Inflammation and Immune Related Diseases of Ministry of Education, Southern Medical University, Guangzhou 510515, China; Guangdong Basic Research Center of Excellence for Integrated Traditional and Western Medicine for Qingzhi Diseases, Guangzhou 510515, China; Corresponding author at: Guangdong Provincial Key Laboratory of New Drug Screening, NMPA Key Laboratory of Drug Metabolism Research and Evaluation, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China.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.http://www.sciencedirect.com/science/article/pii/S1043661824004705Lupus nephritisYin Yang 1 (YY1)T lymphocyteDrug screenRebamipideInflammation |
| spellingShingle | Haoxing Yuan Zheng Peng Meilian Zhang Honglian Li Kunyu Lu Chan Yang Minmin Li Shuwen Liu Antagonising Yin Yang 1 ameliorates the symptoms of lupus nephritis via modulating T lymphocyte signaling Pharmacological Research Lupus nephritis Yin Yang 1 (YY1) T lymphocyte Drug screen Rebamipide Inflammation |
| title | Antagonising Yin Yang 1 ameliorates the symptoms of lupus nephritis via modulating T lymphocyte signaling |
| title_full | Antagonising Yin Yang 1 ameliorates the symptoms of lupus nephritis via modulating T lymphocyte signaling |
| title_fullStr | Antagonising Yin Yang 1 ameliorates the symptoms of lupus nephritis via modulating T lymphocyte signaling |
| title_full_unstemmed | Antagonising Yin Yang 1 ameliorates the symptoms of lupus nephritis via modulating T lymphocyte signaling |
| title_short | Antagonising Yin Yang 1 ameliorates the symptoms of lupus nephritis via modulating T lymphocyte signaling |
| title_sort | antagonising yin yang 1 ameliorates the symptoms of lupus nephritis via modulating t lymphocyte signaling |
| topic | Lupus nephritis Yin Yang 1 (YY1) T lymphocyte Drug screen Rebamipide Inflammation |
| url | http://www.sciencedirect.com/science/article/pii/S1043661824004705 |
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