Fate alteration of bone marrow-derived macrophages ameliorates kidney fibrosis in murine model of unilateral ureteral obstruction
| Autor: | Ziyan Zhang, Ying Yang, Hai-Long Wang, Xiaojian Feng, Xi Qiao, Xinyan Liu, Ying Wang, Jianlin Zhang, Lihua Wang, Guoping Zheng, Linxia Zhao, Min Hu, Rui Guo, Qi Cao |
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| Rok vydání: | 2018 |
| Předmět: |
Male
medicine.medical_treatment Anti-Inflammatory Agents 030232 urology & nephrology Inflammation 030204 cardiovascular system & hematology Kidney Mice 03 medical and health sciences 0302 clinical medicine Transforming Growth Factor beta Fibrosis medicine Renal fibrosis Animals beta Catenin Transplantation business.industry Macrophages medicine.disease Mice Inbred C57BL Disease Models Animal medicine.anatomical_structure Cytokine Nephrology Cancer research Cytokines Bone marrow medicine.symptom business Myofibroblast Signal Transduction Ureteral Obstruction Transforming growth factor |
| Zdroj: | Nephrology Dialysis Transplantation. 34:1657-1668 |
| ISSN: | 1460-2385 0931-0509 |
| DOI: | 10.1093/ndt/gfy381 |
| Popis: | BackgroundRenal fibrosis is a key pathological feature and final common pathway leading to end-stage kidney failure in many chronic kidney diseases. Myofibroblast is the master player in renal fibrosis. However, myofibroblasts are heterogeneous. Recent studies show that bone marrow-derived macrophages transform into myofibroblasts by transforming growth factor (TGF)-β-induced macrophage–myofibroblast transition (MMT) in renal fibrosis.MethodsTGF-β signaling was redirected by inhibition of β-catenin/T-cell factor (TCF) to increase β-catenin/Foxo in bone marrow-derived macrophages. A kidney fibrosis model of unilateral ureteral obstruction was performed in EGFP bone marrow chimera mouse. MMT was examined by flow cytometry analysis of GFP+F4/80+α-SMA+ cells from unilateral ureteral obstruction (UUO) kidney, and by immunofluorescent staining of bone marrow-derived macrophages in vitro. Inflammatory and anti-inflammatory cytokines were analysis by enzyme-linked immunosorbent assay.ResultsInhibition of β-catenin/TCF by ICG-001 combined with TGF-β1 treatment increased β-catenin/Foxo1, reduced the MMT and inflammatory cytokine production by bone marrow-derived macrophages, and thereby, reduced kidney fibrosis in the UUO model.ConclusionsOur results demonstrate that diversion of β-catenin from TCF to Foxo1-mediated transcription not only inhibits the β-catenin/TCF-mediated fibrotic effect of TGF-β, but also enhances its anti-inflammatory action, allowing therapeutic use of TGF-β to reduce both inflammation and fibrosis at least partially by changing the fate of bone marrow-derived macrophages. |
| Databáze: | OpenAIRE |
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