Tigulixostat Alleviates Hyperuricemic Nephropathy by Promoting M2 Macrophage Polarization
Lina Xue,1,2,* Qianru Tao,1,2,* Haining Chang,1,* Shu Yan,1 Lei Wang,3 Zefang Zhao,4 Chao Tu1 1Department of Internal Medicine, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu, People’s Republic of China; 2Department of Nephrology, The Third Affiliated...
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Dove Medical Press
2025-01-01
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| Series: | Journal of Inflammation Research |
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| author | Xue L Tao Q Chang H Yan S Wang L Zhao Z Tu C |
| author_facet | Xue L Tao Q Chang H Yan S Wang L Zhao Z Tu C |
| author_sort | Xue L |
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| description | Lina Xue,1,2,* Qianru Tao,1,2,* Haining Chang,1,* Shu Yan,1 Lei Wang,3 Zefang Zhao,4 Chao Tu1 1Department of Internal Medicine, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu, People’s Republic of China; 2Department of Nephrology, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu, People’s Republic of China; 3Nanjing jinyu medical examination laboratory, Nanjing, Jiangsu, People’s Republic of China; 4Hongyi Honor College, Wuhan University, Wuhan, Hubei, People’s Republic of China*These authors contributed equally to this workCorrespondence: Chao Tu, Department of Internal Medicine, The Third Affiliated Hospital of Soochow University, 185 Juqian Road, Changzhou, Jiangsu, 213000, People’s Republic of China, Tel +86 15895073069, Email tcmedical21@czfph.comPurpose: Serum uric acid (SUA) is primarily produced through the hydrolysis of purines in the liver, with its excretion largely handled by the kidneys. Urate transporter 1 (URAT1) inhibitors are known to enhance uric acid elimination via the kidneys, but they also increase the risk of kidney stone formation. Currently, xanthine oxidase (XO) inhibitors are the predominant uric-lowering medications on the market.Methods: In this study, we utilized single-cell RNA sequencing, spatial metabolomics, plasma metabolomics, flow cytometry to explore the effects of Tigulixostat on uric acid level and hyperuricemic nephropathy (HN) in Uox-KO mouse model.Results: In this study, we discovered that Tigulixostat (LC350189) more effectively reduced SUA levels and resulted in better renal outcomes compared to allopurinol, without inducing liver injury in urate oxidase knockout (Uox-KO) mice. Mechanistically, we found that Tigulixostat improved HN by promoting M2 macrophage polarization.Conclusion: These findings suggest Tigulixostat as a promising therapeutic option for managing hyperuricemia and related kidney conditions. Keywords: hyperuricemic nephropathy, Uox-KO, tigulixostat, Single-cell RNA sequencing, macrophage |
| format | Article |
| id | doaj-art-436898910a1442a495baeb5c4f6d104a |
| institution | Kabale University |
| issn | 1178-7031 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Dove Medical Press |
| record_format | Article |
| series | Journal of Inflammation Research |
| spelling | doaj-art-436898910a1442a495baeb5c4f6d104a2025-01-05T16:36:04ZengDove Medical PressJournal of Inflammation Research1178-70312025-01-01Volume 18173098940Tigulixostat Alleviates Hyperuricemic Nephropathy by Promoting M2 Macrophage PolarizationXue LTao QChang HYan SWang LZhao ZTu CLina Xue,1,2,* Qianru Tao,1,2,* Haining Chang,1,* Shu Yan,1 Lei Wang,3 Zefang Zhao,4 Chao Tu1 1Department of Internal Medicine, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu, People’s Republic of China; 2Department of Nephrology, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu, People’s Republic of China; 3Nanjing jinyu medical examination laboratory, Nanjing, Jiangsu, People’s Republic of China; 4Hongyi Honor College, Wuhan University, Wuhan, Hubei, People’s Republic of China*These authors contributed equally to this workCorrespondence: Chao Tu, Department of Internal Medicine, The Third Affiliated Hospital of Soochow University, 185 Juqian Road, Changzhou, Jiangsu, 213000, People’s Republic of China, Tel +86 15895073069, Email tcmedical21@czfph.comPurpose: Serum uric acid (SUA) is primarily produced through the hydrolysis of purines in the liver, with its excretion largely handled by the kidneys. Urate transporter 1 (URAT1) inhibitors are known to enhance uric acid elimination via the kidneys, but they also increase the risk of kidney stone formation. Currently, xanthine oxidase (XO) inhibitors are the predominant uric-lowering medications on the market.Methods: In this study, we utilized single-cell RNA sequencing, spatial metabolomics, plasma metabolomics, flow cytometry to explore the effects of Tigulixostat on uric acid level and hyperuricemic nephropathy (HN) in Uox-KO mouse model.Results: In this study, we discovered that Tigulixostat (LC350189) more effectively reduced SUA levels and resulted in better renal outcomes compared to allopurinol, without inducing liver injury in urate oxidase knockout (Uox-KO) mice. Mechanistically, we found that Tigulixostat improved HN by promoting M2 macrophage polarization.Conclusion: These findings suggest Tigulixostat as a promising therapeutic option for managing hyperuricemia and related kidney conditions. Keywords: hyperuricemic nephropathy, Uox-KO, tigulixostat, Single-cell RNA sequencing, macrophagehttps://www.dovepress.com/tigulixostat-alleviates-hyperuricemic-nephropathy-by-promoting-m2-macr-peer-reviewed-fulltext-article-JIRhyperuricemic nephropathyuox-kotigulixostatsingle-cell rna sequencingmacrophage |
| spellingShingle | Xue L Tao Q Chang H Yan S Wang L Zhao Z Tu C Tigulixostat Alleviates Hyperuricemic Nephropathy by Promoting M2 Macrophage Polarization Journal of Inflammation Research hyperuricemic nephropathy uox-ko tigulixostat single-cell rna sequencing macrophage |
| title | Tigulixostat Alleviates Hyperuricemic Nephropathy by Promoting M2 Macrophage Polarization |
| title_full | Tigulixostat Alleviates Hyperuricemic Nephropathy by Promoting M2 Macrophage Polarization |
| title_fullStr | Tigulixostat Alleviates Hyperuricemic Nephropathy by Promoting M2 Macrophage Polarization |
| title_full_unstemmed | Tigulixostat Alleviates Hyperuricemic Nephropathy by Promoting M2 Macrophage Polarization |
| title_short | Tigulixostat Alleviates Hyperuricemic Nephropathy by Promoting M2 Macrophage Polarization |
| title_sort | tigulixostat alleviates hyperuricemic nephropathy by promoting m2 macrophage polarization |
| topic | hyperuricemic nephropathy uox-ko tigulixostat single-cell rna sequencing macrophage |
| url | https://www.dovepress.com/tigulixostat-alleviates-hyperuricemic-nephropathy-by-promoting-m2-macr-peer-reviewed-fulltext-article-JIR |
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