Macrophage polarization induces endothelium-to-myofibroblast transition in chronic allograft dysfunction
Our research explores the role of M1 macrophage polarization in endothelium-to-myofibroblast transition (EndMT) and chronic allograft dysfunction (CAD). GSE21374 transcriptome sequencing data were obtained. Transplanted nephrectomy specimens from CAD patients were collected and studied to explore th...
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2023-12-01
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| Series: | Renal Failure |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/0886022X.2023.2220418 |
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| author | Zeping Gui Xiang Zhang Qianguang Han Zhou Hang Ruoyun Tan Min Gu Zijie Wang |
| author_facet | Zeping Gui Xiang Zhang Qianguang Han Zhou Hang Ruoyun Tan Min Gu Zijie Wang |
| author_sort | Zeping Gui |
| collection | DOAJ |
| description | Our research explores the role of M1 macrophage polarization in endothelium-to-myofibroblast transition (EndMT) and chronic allograft dysfunction (CAD). GSE21374 transcriptome sequencing data were obtained. Transplanted nephrectomy specimens from CAD patients were collected and studied to explore the infiltration of M1 and M2 macrophages using immunofluorescence, PCR, and Western blotting (WB). A co-culture model of M1 macrophages, polarized from mouse bone marrow-derived macrophages (BMDM) or Raw264.7, and aortic endothelial cells was established, and EndMT was tested using PCR and WB. RNA-sequencing was performed on the macrophages from the mouse BMDM. The TNF-α secreted from the polarized M1 macrophages was verified using ELISA. Based on the GEO public database, it was observed that macrophages were significantly infiltrated in CAD allograft tissues, with CD68(+) iNOS(+) M1 macrophages significantly infiltrating the glomeruli of allograft tissues, and CD68(+)CD206(+) M2 macrophages notably infiltrating the allograft interstitial area. The mRNA expression of the M1 macrophage marker inducible nitric oxide synthase (iNOS) was significantly increased (p < 0.05) and M1 macrophages were found to significantly promote the EndMT process in vitro. RNA-Sequencing analysis revealed that TNF signaling could be involved in the EndMT induced by M1 macrophages, and in vitro studies confirmed that TNF-α in the supernatant was significantly higher. The renal allograft tissues of CAD patients were found to be significantly infiltrated by M1 macrophages and could promote the progression of CAD by secreting the cytokine TNF-α to induce EndMT in endothelial cells. |
| format | Article |
| id | doaj-art-e3c647afcff54270bc8dd4a7f54779f4 |
| institution | OA Journals |
| issn | 0886-022X 1525-6049 |
| language | English |
| publishDate | 2023-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Renal Failure |
| spelling | doaj-art-e3c647afcff54270bc8dd4a7f54779f42025-08-20T02:16:10ZengTaylor & Francis GroupRenal Failure0886-022X1525-60492023-12-0145110.1080/0886022X.2023.2220418Macrophage polarization induces endothelium-to-myofibroblast transition in chronic allograft dysfunctionZeping Gui0Xiang Zhang1Qianguang Han2Zhou Hang3Ruoyun Tan4Min Gu5Zijie Wang6Department of Urology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, P.R. ChinaDepartment of Urology, The Affiliated Hospital of Nantong University, Nantong, P.R. ChinaDepartment of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, P.R. ChinaDepartment of Urology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, P.R. ChinaDepartment of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, P.R. ChinaDepartment of Urology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, P.R. ChinaDepartment of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, P.R. ChinaOur research explores the role of M1 macrophage polarization in endothelium-to-myofibroblast transition (EndMT) and chronic allograft dysfunction (CAD). GSE21374 transcriptome sequencing data were obtained. Transplanted nephrectomy specimens from CAD patients were collected and studied to explore the infiltration of M1 and M2 macrophages using immunofluorescence, PCR, and Western blotting (WB). A co-culture model of M1 macrophages, polarized from mouse bone marrow-derived macrophages (BMDM) or Raw264.7, and aortic endothelial cells was established, and EndMT was tested using PCR and WB. RNA-sequencing was performed on the macrophages from the mouse BMDM. The TNF-α secreted from the polarized M1 macrophages was verified using ELISA. Based on the GEO public database, it was observed that macrophages were significantly infiltrated in CAD allograft tissues, with CD68(+) iNOS(+) M1 macrophages significantly infiltrating the glomeruli of allograft tissues, and CD68(+)CD206(+) M2 macrophages notably infiltrating the allograft interstitial area. The mRNA expression of the M1 macrophage marker inducible nitric oxide synthase (iNOS) was significantly increased (p < 0.05) and M1 macrophages were found to significantly promote the EndMT process in vitro. RNA-Sequencing analysis revealed that TNF signaling could be involved in the EndMT induced by M1 macrophages, and in vitro studies confirmed that TNF-α in the supernatant was significantly higher. The renal allograft tissues of CAD patients were found to be significantly infiltrated by M1 macrophages and could promote the progression of CAD by secreting the cytokine TNF-α to induce EndMT in endothelial cells.https://www.tandfonline.com/doi/10.1080/0886022X.2023.2220418Macrophagespolarizationendothelium-to-myofibroblast transitionchronic allograft dysfunctionTNF-α |
| spellingShingle | Zeping Gui Xiang Zhang Qianguang Han Zhou Hang Ruoyun Tan Min Gu Zijie Wang Macrophage polarization induces endothelium-to-myofibroblast transition in chronic allograft dysfunction Renal Failure Macrophages polarization endothelium-to-myofibroblast transition chronic allograft dysfunction TNF-α |
| title | Macrophage polarization induces endothelium-to-myofibroblast transition in chronic allograft dysfunction |
| title_full | Macrophage polarization induces endothelium-to-myofibroblast transition in chronic allograft dysfunction |
| title_fullStr | Macrophage polarization induces endothelium-to-myofibroblast transition in chronic allograft dysfunction |
| title_full_unstemmed | Macrophage polarization induces endothelium-to-myofibroblast transition in chronic allograft dysfunction |
| title_short | Macrophage polarization induces endothelium-to-myofibroblast transition in chronic allograft dysfunction |
| title_sort | macrophage polarization induces endothelium to myofibroblast transition in chronic allograft dysfunction |
| topic | Macrophages polarization endothelium-to-myofibroblast transition chronic allograft dysfunction TNF-α |
| url | https://www.tandfonline.com/doi/10.1080/0886022X.2023.2220418 |
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