M2 macrophage infusion ameliorates diabetic glomerulopathy via the JAK2/STAT3 pathway in db/db mice
Objectives: To explore the therapeutic effects of M2 macrophages in diabetic nephropathy (DN) and their mechanism.Methods: We infused M2 macrophages stimulated with IL-4 into 10-week-old db/db mice once a week for 4 weeks through the tail vein as M2 group. Then we investigated the role of M2 macroph...
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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.2024.2378210 |
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| author | Yulin Gu Songyan Yu Weijun Gu Bing Li Jing Xue Jiejie Liu Qi Zhang Yaqi Yin Haixia Zhang Qinghua Guo Mingxia Yuan Zhaohui Lyu Yiming Mu Yu Cheng |
| author_facet | Yulin Gu Songyan Yu Weijun Gu Bing Li Jing Xue Jiejie Liu Qi Zhang Yaqi Yin Haixia Zhang Qinghua Guo Mingxia Yuan Zhaohui Lyu Yiming Mu Yu Cheng |
| author_sort | Yulin Gu |
| collection | DOAJ |
| description | Objectives: To explore the therapeutic effects of M2 macrophages in diabetic nephropathy (DN) and their mechanism.Methods: We infused M2 macrophages stimulated with IL-4 into 10-week-old db/db mice once a week for 4 weeks through the tail vein as M2 group. Then we investigated the role of M2 macrophages in alleviating the infammation of DN and explored the mechanism.Results: M2 macrophages hindered the progression of DN, reduced the levels of IL-1β (DN group was 34%, M2 group was 13%, p < 0.01) and MCP-1 (DN group was 49%, M2 group was 16%, p < 0.01) in the glomeruli. It was also proven that M2 macrophages alleviate mesangial cell injury caused by a high glucose environment. M2 macrophage tracking showed that the infused M2 macrophages migrated to the kidney, and the number of M2 macrophages in the kidney reached a maximum on day 3. Moreover, the ratio of M2 to M1 macrophages was 2.3 in the M2 infusion group, while 0.4 in the DN group (p < 0.01). Mechanistically, M2 macrophages downregulated Janus kinase (JAK) 2 and signal transducer and activator of transcription (STAT) 3 in mesangial cells.Conclusions: Multiple infusions of M2 macrophages significantly alleviated inflammation in the kidney and hindered the progression of DN at least partially by abrogating the M1/M2 homeostasis disturbances and suppressing the JAK2/STAT3 pathway in glomerular mesangial cells. M2 macrophage infusion may be a new therapeutic strategy for DN treatment. |
| format | Article |
| id | doaj-art-382415fa237e43b4b5e522c7a76b06a3 |
| institution | DOAJ |
| issn | 0886-022X 1525-6049 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Renal Failure |
| spelling | doaj-art-382415fa237e43b4b5e522c7a76b06a32025-08-20T03:05:34ZengTaylor & Francis GroupRenal Failure0886-022X1525-60492024-12-0146210.1080/0886022X.2024.2378210M2 macrophage infusion ameliorates diabetic glomerulopathy via the JAK2/STAT3 pathway in db/db miceYulin Gu0Songyan Yu1Weijun Gu2Bing Li3Jing Xue4Jiejie Liu5Qi Zhang6Yaqi Yin7Haixia Zhang8Qinghua Guo9Mingxia Yuan10Zhaohui Lyu11Yiming Mu12Yu Cheng13Department of Endocrinology, Beijing Friendship Hospital, Capital Medical University, Beijing, ChinaDepartment of Endocrinology, Beijing Tiantan Hospital, Capital Medical University, Beijing, ChinaDepartment of Endocrinology, Medical School of Chinese PLA, Chinese PLA General Hospital, Beijing, ChinaDepartment of Endocrinology, Medical School of Chinese PLA, Chinese PLA General Hospital, Beijing, ChinaDepartment of Endocrinology, Medical School of Chinese PLA, Chinese PLA General Hospital, Beijing, ChinaDepartment of Molecular Biology, Institute of Basic Medicine, School of Life Science, Chinese PLA General Hospital, Beijing, ChinaDepartment of Endocrinology, Beijing Tiantan Hospital, Capital Medical University, Beijing, ChinaDepartment of Endocrinology, Medical School of Chinese PLA, Chinese PLA General Hospital, Beijing, ChinaDepartment of Endocrinology, Medical School of Chinese PLA, Chinese PLA General Hospital, Beijing, ChinaDepartment of Endocrinology, Medical School of Chinese PLA, Chinese PLA General Hospital, Beijing, ChinaDepartment of Endocrinology, Beijing Friendship Hospital, Capital Medical University, Beijing, ChinaDepartment of Endocrinology, Medical School of Chinese PLA, Chinese PLA General Hospital, Beijing, ChinaDepartment of Endocrinology, Medical School of Chinese PLA, Chinese PLA General Hospital, Beijing, ChinaDepartment of Endocrinology, Medical School of Chinese PLA, Chinese PLA General Hospital, Beijing, ChinaObjectives: To explore the therapeutic effects of M2 macrophages in diabetic nephropathy (DN) and their mechanism.Methods: We infused M2 macrophages stimulated with IL-4 into 10-week-old db/db mice once a week for 4 weeks through the tail vein as M2 group. Then we investigated the role of M2 macrophages in alleviating the infammation of DN and explored the mechanism.Results: M2 macrophages hindered the progression of DN, reduced the levels of IL-1β (DN group was 34%, M2 group was 13%, p < 0.01) and MCP-1 (DN group was 49%, M2 group was 16%, p < 0.01) in the glomeruli. It was also proven that M2 macrophages alleviate mesangial cell injury caused by a high glucose environment. M2 macrophage tracking showed that the infused M2 macrophages migrated to the kidney, and the number of M2 macrophages in the kidney reached a maximum on day 3. Moreover, the ratio of M2 to M1 macrophages was 2.3 in the M2 infusion group, while 0.4 in the DN group (p < 0.01). Mechanistically, M2 macrophages downregulated Janus kinase (JAK) 2 and signal transducer and activator of transcription (STAT) 3 in mesangial cells.Conclusions: Multiple infusions of M2 macrophages significantly alleviated inflammation in the kidney and hindered the progression of DN at least partially by abrogating the M1/M2 homeostasis disturbances and suppressing the JAK2/STAT3 pathway in glomerular mesangial cells. M2 macrophage infusion may be a new therapeutic strategy for DN treatment.https://www.tandfonline.com/doi/10.1080/0886022X.2024.2378210Diabetic complicationdiabetic nephropathyM2 macrophagesinflammationJAK2/STAT3 pathway |
| spellingShingle | Yulin Gu Songyan Yu Weijun Gu Bing Li Jing Xue Jiejie Liu Qi Zhang Yaqi Yin Haixia Zhang Qinghua Guo Mingxia Yuan Zhaohui Lyu Yiming Mu Yu Cheng M2 macrophage infusion ameliorates diabetic glomerulopathy via the JAK2/STAT3 pathway in db/db mice Renal Failure Diabetic complication diabetic nephropathy M2 macrophages inflammation JAK2/STAT3 pathway |
| title | M2 macrophage infusion ameliorates diabetic glomerulopathy via the JAK2/STAT3 pathway in db/db mice |
| title_full | M2 macrophage infusion ameliorates diabetic glomerulopathy via the JAK2/STAT3 pathway in db/db mice |
| title_fullStr | M2 macrophage infusion ameliorates diabetic glomerulopathy via the JAK2/STAT3 pathway in db/db mice |
| title_full_unstemmed | M2 macrophage infusion ameliorates diabetic glomerulopathy via the JAK2/STAT3 pathway in db/db mice |
| title_short | M2 macrophage infusion ameliorates diabetic glomerulopathy via the JAK2/STAT3 pathway in db/db mice |
| title_sort | m2 macrophage infusion ameliorates diabetic glomerulopathy via the jak2 stat3 pathway in db db mice |
| topic | Diabetic complication diabetic nephropathy M2 macrophages inflammation JAK2/STAT3 pathway |
| url | https://www.tandfonline.com/doi/10.1080/0886022X.2024.2378210 |
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