Iguratimod prevents renal fibrosis in unilateral ureteral obstruction model mice by suppressing M2 macrophage infiltration and macrophage–myofibroblast transition
Iguratimod is a novel synthetic, small-molecule immunosuppressive agent used to treat rheumatoid arthritis. Through ongoing exploration of its role and mechanisms of action, iguratimod has been observed to have antifibrotic effects in the lung and skin; however, its effect on renal fibrosis remains...
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2024-12-01
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| Series: | Renal Failure |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/0886022X.2024.2327498 |
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| _version_ | 1832591126761046016 |
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| author | Yueyuan Zhou Zhilan Li Shenyi Yu Xuan Wang Tingting Xie Weiru Zhang |
| author_facet | Yueyuan Zhou Zhilan Li Shenyi Yu Xuan Wang Tingting Xie Weiru Zhang |
| author_sort | Yueyuan Zhou |
| collection | DOAJ |
| description | Iguratimod is a novel synthetic, small-molecule immunosuppressive agent used to treat rheumatoid arthritis. Through ongoing exploration of its role and mechanisms of action, iguratimod has been observed to have antifibrotic effects in the lung and skin; however, its effect on renal fibrosis remains unknown. This study aimed to investigate whether iguratimod could affect renal fibrosis progression. Three different concentrations of iguratimod (30 mg/kg/day, 10 mg/kg/day, and 3 mg/kg/day) were used to intervene in unilateral ureteral obstruction (UUO) model mice. Iguratimod at 10 mg/kg/day was observed to be effective in slowing UUO-mediated renal fibrosis. In addition, stimulating bone marrow-derived macrophages with IL-4 and/or iguratimod, or with TGF-β and iguratimod or SRC inhibitors in vitro, suggested that iguratimod mitigates the progression of renal fibrosis in UUO mice, at least in part, by inhibiting the IL-4/STAT6 signaling pathway to attenuate renal M2 macrophage infiltration, as well as by impeding SRC activation to reduce macrophage–myofibroblast transition. These findings reveal the potential of iguratimod as a treatment for renal disease. |
| format | Article |
| id | doaj-art-c78f9d5d7a3245ca854071fcf65e8e2b |
| institution | Kabale University |
| issn | 0886-022X 1525-6049 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Renal Failure |
| spelling | doaj-art-c78f9d5d7a3245ca854071fcf65e8e2b2025-01-23T04:17:49ZengTaylor & Francis GroupRenal Failure0886-022X1525-60492024-12-0146110.1080/0886022X.2024.2327498Iguratimod prevents renal fibrosis in unilateral ureteral obstruction model mice by suppressing M2 macrophage infiltration and macrophage–myofibroblast transitionYueyuan Zhou0Zhilan Li1Shenyi Yu2Xuan Wang3Tingting Xie4Weiru Zhang5Department of General Medicine, Xiangya Hospital, Central South University, Changsha, ChinaDepartment of General Medicine, Xiangya Hospital, Central South University, Changsha, ChinaDepartment of Rheumatology and Immunology, Zhuzhou Hospital Affiliated to Xiangya Medical College, Central South University, Zhuzhou, ChinaDepartment of General Medicine, Xiangya Hospital, Central South University, Changsha, ChinaDepartment of General Medicine, Xiangya Hospital, Central South University, Changsha, ChinaDepartment of General Medicine, Xiangya Hospital, Central South University, Changsha, ChinaIguratimod is a novel synthetic, small-molecule immunosuppressive agent used to treat rheumatoid arthritis. Through ongoing exploration of its role and mechanisms of action, iguratimod has been observed to have antifibrotic effects in the lung and skin; however, its effect on renal fibrosis remains unknown. This study aimed to investigate whether iguratimod could affect renal fibrosis progression. Three different concentrations of iguratimod (30 mg/kg/day, 10 mg/kg/day, and 3 mg/kg/day) were used to intervene in unilateral ureteral obstruction (UUO) model mice. Iguratimod at 10 mg/kg/day was observed to be effective in slowing UUO-mediated renal fibrosis. In addition, stimulating bone marrow-derived macrophages with IL-4 and/or iguratimod, or with TGF-β and iguratimod or SRC inhibitors in vitro, suggested that iguratimod mitigates the progression of renal fibrosis in UUO mice, at least in part, by inhibiting the IL-4/STAT6 signaling pathway to attenuate renal M2 macrophage infiltration, as well as by impeding SRC activation to reduce macrophage–myofibroblast transition. These findings reveal the potential of iguratimod as a treatment for renal disease.https://www.tandfonline.com/doi/10.1080/0886022X.2024.2327498Iguratimodmacrophage infiltrationmacrophage–myofibroblast transitionrenal fibrosisunilateral ureteral obstruction |
| spellingShingle | Yueyuan Zhou Zhilan Li Shenyi Yu Xuan Wang Tingting Xie Weiru Zhang Iguratimod prevents renal fibrosis in unilateral ureteral obstruction model mice by suppressing M2 macrophage infiltration and macrophage–myofibroblast transition Renal Failure Iguratimod macrophage infiltration macrophage–myofibroblast transition renal fibrosis unilateral ureteral obstruction |
| title | Iguratimod prevents renal fibrosis in unilateral ureteral obstruction model mice by suppressing M2 macrophage infiltration and macrophage–myofibroblast transition |
| title_full | Iguratimod prevents renal fibrosis in unilateral ureteral obstruction model mice by suppressing M2 macrophage infiltration and macrophage–myofibroblast transition |
| title_fullStr | Iguratimod prevents renal fibrosis in unilateral ureteral obstruction model mice by suppressing M2 macrophage infiltration and macrophage–myofibroblast transition |
| title_full_unstemmed | Iguratimod prevents renal fibrosis in unilateral ureteral obstruction model mice by suppressing M2 macrophage infiltration and macrophage–myofibroblast transition |
| title_short | Iguratimod prevents renal fibrosis in unilateral ureteral obstruction model mice by suppressing M2 macrophage infiltration and macrophage–myofibroblast transition |
| title_sort | iguratimod prevents renal fibrosis in unilateral ureteral obstruction model mice by suppressing m2 macrophage infiltration and macrophage myofibroblast transition |
| topic | Iguratimod macrophage infiltration macrophage–myofibroblast transition renal fibrosis unilateral ureteral obstruction |
| url | https://www.tandfonline.com/doi/10.1080/0886022X.2024.2327498 |
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