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Updated: Oct 1, 2025
Phenotypic Characterization of Macrophages from Rat Kidney by Flow Cytometry
Published on: October 18, 2016
Pharmacological targeting macrophage phenotype via gut-kidney axis ameliorates renal fibrosis in mice
Yanan Xie1, Xiaofan Hu1, Shanglin Li1
1Institute of Organ Transplantation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, China.
Abstract:
Renal fibrosis is a non-negligible pathological change in chronic kidney disease (CKD). Increasing evidence indicates that macrophage and gut-kidney axis are correlated with CKD. In this study, we manifest that pharmacological modulating macrophage phenotype via gut-kidney axis is conducive to the alleviation of renal fibrosis. Employing wild-type male mice with unilateral ureteral obstruction (UUO), renal fibrosis was dramatically mitigated in mice treated with antibiotics. And antibiotics application restricted the synthesis of intestinal flora metabolite Trimethylamine N-Oxide (TMAO). However, a 1.3% choline diet enhanced fibrosis. Then we further examined macrophage phenotype through the gut-kidney axis. In in vivo and in vitro culture experiments, the mRNA expression of Nos2, Tnf-α, Il-6, and Il-1β increased under TMAO stimulation. Curbing the NLRP3 inflammasome countered TMAO-induced M1 polarization in bone marrow-derived macrophages. This finding demonstrates that NLRP3 plays a critical part in macrophage polarization. Because of the declining M1 polarization trend in the early stage, M2 macrophages undoubtedly decreased in the tissues. Our results revealed that some metabolites could regulate macrophage phenotype, which matters the severity of renal fibrosis. Thus, pharmacological targeting macrophage phenotype via gut-kidney axis may be a different strategy to treat renal fibrosis.
Insights
Targeting macrophage polarization through the gut-kidney axis can alleviate renal fibrosis in chronic kidney disease (CKD). Modulating gut microbiota metabolites like Trimethylamine N-Oxide (TMAO) impacts macrophage phenotypes and fibrosis severity.
Area of Science:
- Nephrology
- Immunology
- Microbiology
Background:
- Renal fibrosis is a key pathological feature of chronic kidney disease (CKD).
- The gut-kidney axis and macrophage polarization are increasingly recognized as critical factors in CKD progression.
Purpose of the Study:
- To investigate the role of the gut-kidney axis in modulating macrophage phenotype for the alleviation of renal fibrosis.
- To explore the impact of gut microbiota metabolites, specifically Trimethylamine N-Oxide (TMAO), on macrophage polarization and renal fibrosis.
Main Methods:
- Utilized a unilateral ureteral obstruction (UUO) mouse model to induce renal fibrosis.
- Administered antibiotics to modulate gut microbiota and assessed the effects on fibrosis and TMAO levels.
- Investigated macrophage polarization in vivo and in vitro under TMAO stimulation.
- Examined the role of the NLRP3 inflammasome in TMAO-induced macrophage polarization.
Main Results:
- Antibiotic treatment significantly mitigated renal fibrosis in the UUO model by reducing TMAO synthesis.
- A high choline diet, which increases TMAO, exacerbated renal fibrosis.
- TMAO stimulation promoted M1 macrophage polarization and increased pro-inflammatory cytokine expression (Nos2, Tnf-α, Il-6, Il-1β).
- Inhibition of the NLRP3 inflammasome effectively countered TMAO-induced M1 polarization.
Conclusions:
- Gut microbiota metabolites, such as TMAO, significantly influence macrophage polarization and contribute to renal fibrosis severity.
- Targeting macrophage phenotype modulation via the gut-kidney axis presents a potential therapeutic strategy for renal fibrosis in CKD.
