Suppressor of Cytokine Signaling-1/STAT1 Regulates Renal Inflammation in Mesangial Proliferative Glomerulonephritis Models
Mesangial proliferative glomerulonephritis (MsGN) is a significant global threat to public health. Inflammation plays a crucial role in MsGN; however, the underlying mechanism remains unknown. Herein, we demonstrate that suppression of the cytokine signaling-1 (SOCS1)/signal transducer and activator...
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Frontiers Media S.A.
2018-08-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2018.01982/full |
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| author | Jiuxu Bai Lingling Wu Xiaoniao Chen Liqiang Wang Qinggang Li Yingjie Zhang Jie Wu Guangyan Cai Xiangmei Chen |
| author_facet | Jiuxu Bai Lingling Wu Xiaoniao Chen Liqiang Wang Qinggang Li Yingjie Zhang Jie Wu Guangyan Cai Xiangmei Chen |
| author_sort | Jiuxu Bai |
| collection | DOAJ |
| description | Mesangial proliferative glomerulonephritis (MsGN) is a significant global threat to public health. Inflammation plays a crucial role in MsGN; however, the underlying mechanism remains unknown. Herein, we demonstrate that suppression of the cytokine signaling-1 (SOCS1)/signal transducer and activator of transcription 1 (STAT1) signaling pathway is associated with renal inflammation and renal injury in MsGN. Using MsGN rat (Thy1.1 GN) and mouse (Habu GN) models, renal SOCS1/STAT1 was determined to be associated with CD4+ T cell infiltration and related cytokines. In vitro, SOCS1 overexpression repressed IFN-γ-induced MHC class II and cytokine levels and STAT1 phosphorylation in mesangial cells. SOCS1 and STAT1 inhibitors significantly inhibited IFN-γ-induced CIITA promoter activity and MHC class II expression. In conclusion, our study emphasizes the pivotal role of the SOCS1/STAT1 axis in the regulation of inflammation in MsGN. |
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| format | Article |
| id | doaj.art-859f0a1ed61d4e739ec4597a227996cd |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-13T09:15:33Z |
| publishDate | 2018-08-01 |
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| series | Frontiers in Immunology |
| spelling | doaj.art-859f0a1ed61d4e739ec4597a227996cd2022-12-22T02:52:45ZengFrontiers Media S.A.Frontiers in Immunology1664-32242018-08-01910.3389/fimmu.2018.01982389810Suppressor of Cytokine Signaling-1/STAT1 Regulates Renal Inflammation in Mesangial Proliferative Glomerulonephritis ModelsJiuxu Bai0Lingling Wu1Xiaoniao Chen2Liqiang Wang3Qinggang Li4Yingjie Zhang5Jie Wu6Guangyan Cai7Xiangmei Chen8State Key Laboratory of Kidney Diseases, Department of Nephrology, National Clinical Research Center for Kidney Diseases, Chinese PLA General Hospital, Chinese PLA Institute of Nephrology, Beijing, ChinaState Key Laboratory of Kidney Diseases, Department of Nephrology, National Clinical Research Center for Kidney Diseases, Chinese PLA General Hospital, Chinese PLA Institute of Nephrology, Beijing, ChinaDepartment of Ophthalmology, Ophthalmology and Visual Science Key Lab of PLA, Chinese PLA General Hospital, Beijing, ChinaDepartment of Ophthalmology, Ophthalmology and Visual Science Key Lab of PLA, Chinese PLA General Hospital, Beijing, ChinaState Key Laboratory of Kidney Diseases, Department of Nephrology, National Clinical Research Center for Kidney Diseases, Chinese PLA General Hospital, Chinese PLA Institute of Nephrology, Beijing, ChinaState Key Laboratory of Kidney Diseases, Department of Nephrology, National Clinical Research Center for Kidney Diseases, Chinese PLA General Hospital, Chinese PLA Institute of Nephrology, Beijing, ChinaState Key Laboratory of Kidney Diseases, Department of Nephrology, National Clinical Research Center for Kidney Diseases, Chinese PLA General Hospital, Chinese PLA Institute of Nephrology, Beijing, ChinaState Key Laboratory of Kidney Diseases, Department of Nephrology, National Clinical Research Center for Kidney Diseases, Chinese PLA General Hospital, Chinese PLA Institute of Nephrology, Beijing, ChinaState Key Laboratory of Kidney Diseases, Department of Nephrology, National Clinical Research Center for Kidney Diseases, Chinese PLA General Hospital, Chinese PLA Institute of Nephrology, Beijing, ChinaMesangial proliferative glomerulonephritis (MsGN) is a significant global threat to public health. Inflammation plays a crucial role in MsGN; however, the underlying mechanism remains unknown. Herein, we demonstrate that suppression of the cytokine signaling-1 (SOCS1)/signal transducer and activator of transcription 1 (STAT1) signaling pathway is associated with renal inflammation and renal injury in MsGN. Using MsGN rat (Thy1.1 GN) and mouse (Habu GN) models, renal SOCS1/STAT1 was determined to be associated with CD4+ T cell infiltration and related cytokines. In vitro, SOCS1 overexpression repressed IFN-γ-induced MHC class II and cytokine levels and STAT1 phosphorylation in mesangial cells. SOCS1 and STAT1 inhibitors significantly inhibited IFN-γ-induced CIITA promoter activity and MHC class II expression. In conclusion, our study emphasizes the pivotal role of the SOCS1/STAT1 axis in the regulation of inflammation in MsGN.https://www.frontiersin.org/article/10.3389/fimmu.2018.01982/fullinflammationmesangial proliferative glomerulonephritisSOCS1STAT1MHC class II |
| spellingShingle | Jiuxu Bai Lingling Wu Xiaoniao Chen Liqiang Wang Qinggang Li Yingjie Zhang Jie Wu Guangyan Cai Xiangmei Chen Suppressor of Cytokine Signaling-1/STAT1 Regulates Renal Inflammation in Mesangial Proliferative Glomerulonephritis Models Frontiers in Immunology inflammation mesangial proliferative glomerulonephritis SOCS1 STAT1 MHC class II |
| title | Suppressor of Cytokine Signaling-1/STAT1 Regulates Renal Inflammation in Mesangial Proliferative Glomerulonephritis Models |
| title_full | Suppressor of Cytokine Signaling-1/STAT1 Regulates Renal Inflammation in Mesangial Proliferative Glomerulonephritis Models |
| title_fullStr | Suppressor of Cytokine Signaling-1/STAT1 Regulates Renal Inflammation in Mesangial Proliferative Glomerulonephritis Models |
| title_full_unstemmed | Suppressor of Cytokine Signaling-1/STAT1 Regulates Renal Inflammation in Mesangial Proliferative Glomerulonephritis Models |
| title_short | Suppressor of Cytokine Signaling-1/STAT1 Regulates Renal Inflammation in Mesangial Proliferative Glomerulonephritis Models |
| title_sort | suppressor of cytokine signaling 1 stat1 regulates renal inflammation in mesangial proliferative glomerulonephritis models |
| topic | inflammation mesangial proliferative glomerulonephritis SOCS1 STAT1 MHC class II |
| url | https://www.frontiersin.org/article/10.3389/fimmu.2018.01982/full |
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