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Abstract: FR-OR105

The Effects and Potential Role of Circulating Macrophage in Renal Fibrosis

Session Information

Category: CKD (Non-Dialysis)

  • 1903 CKD (Non-Dialysis): Mechanisms

Authors

  • Xu, Gang, Tongji hospital affiliated to Tongji medical college, Huazhong University of Science and Technology, Wuhan, China
  • Wang, Yuxi, Division of Nephrology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology Wuhan, Hubei, China, Wuhan, China
  • Zeng, Rui, Tongji Hospital, Huazhong Univ of Science and Technology, Wuhan, HUBEI, China
Background

Macrophages plays an important role in the process of renal fibrosis. Recent studies have suggested that circulative macrophages are the major source of myofibroblasts, which is contradicted with traditional view, that only a few myofibroblasts were derived from bone marrow-derived cells. In this study, we looked for changes in CKD lesions and macrophages at different stages to find better classification of macrophage

Methods

Firstly, we adopted a bone marrow transplantation (BMT) model using GFP mouse bone marrow cells. Secondly, a parabiosis + I/R model or UUO model was constructed using GFP mice. To further understand the link between macrophage with myofibroblast, CSF1r-GFP mice were adopted in parabiosis + I/R model. Otherwise, we used the chlorophosphate liposome (CL) to knockout macrophages. CCR2-/- mice were adopted to construct parabiosis + I/R models to observe the effect of circulating macrophage in renal fibrosis. To directly explore the mechanism of macrophage on renal injury, we sorted Ly6c+ inflammatory macrophages from I/R kidneys and injected under kidney capsule of immunodeficient mice. At the same time, fibrosis-related markers were detected after co-culture the sorted Ly6c+ cells with fibroblasts.

Results

BMT+I/R model found that 22.55% of renal myofibroblasts were derived from bone marrow-derived cells, and 14.6% of myofibroblasts were derived from peripheral macrophages. The parabiosis + I/R or UUO model by using CSF1r-GFP mice proved that 5-9% of myofibroblasts in the kidney expressed GFP. With the treatment of CL, operated mice had early renal injury and delayed atrophy, and renal tubular injury was alleviated. Then we used CCR2-/- mice and observed that mice knocked out of peripheral macrophages reduced renal fibrosis; CCR2-/- mice were constructed parabiosis model with WT mice, in which peripheral macrophages can be replenished, and their kidney damage and fibrosis are aggravated. The sorted Ly6c+ inflammatory macrophages direcltly lead to increased fibroblast activation and fibrosis.

Conclusion

The results indicated that peripheral derived macrophages are not the main source of myofibroblasts. The sorted Ly6c+ macrophages have the effect on promoting renal fibrosis. Knockout peripheral inflammatory macrophages reduce renal fibrosis. Ly6c+ inflammatory macrophages can directly lead to normal kidney damage and fibrosis and can promote fibroblast activation.

Funding

  • Government Support - Non-U.S.