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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Bibliographic Details
Published in:Renal failure 2023-12, Vol.45 (1), p.2220418-2220418
Main Authors: Gui, Zeping, Zhang, Xiang, Han, Qianguang, Hang, Zhou, Tan, Ruoyun, Gu, Min, Wang, Zijie
Format: Article
Language:English
Subjects:
Allografts
Animals
Aorta
Bone marrow
Cell culture
chronic allograft dysfunction
Endothelial cells
Endothelial Cells - metabolism
Endothelium
Endothelium - metabolism
endothelium-to-myofibroblast transition
Enzyme-linked immunosorbent assay
Gene expression
Immunofluorescence
Kidney transplantation
Kidney Transplantation - adverse effects
Macrophages
Macrophages - metabolism
Mice
Myofibroblasts - metabolism
Nephrectomy
Nitric oxide
Nitric-oxide synthase
Polarization
RNA - metabolism
Sequence analysis
TNF-α
Transcriptomes
Tumor Necrosis Factor-alpha - metabolism
Tumor necrosis factor-α
Western blotting
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Summary: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 
ISSN:0886-022X
1525-6049
DOI:10.1080/0886022X.2023.2220418