Abstract: SA-PO800
Kidney Ly6c- Macrophages Directly Promote Ischemia Induced Renal Fibrosis
Session Information
- Molecular Mechanisms of CKD - III
October 27, 2018 | Location: Exhibit Hall, San Diego Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: CKD (Non-Dialysis)
- 1903 CKD (Non-Dialysis): Mechanisms
Authors
- Yang, Qian, Tongji Hospital, Huazhong Univ of Science and Technology, Wuhan, HuBei , China
- Zeng, Rui, Tongji Hospital, Huazhong Univ of Science and Technology, Wuhan, HuBei , China
- Xu, Gang, Tongji Hospital, Huazhong Univ of Science and Technology, Wuhan, HuBei , China
Background
Macrophages are a plastic and heterogeneous cell type in renal injury, repair and fibrosis in acute kidney injury (AKI) to chronic kidney disease (CKD) progression, but the function of different macrophage population is still elusive.
Methods
In our study, we focused on exploring the function of Ly6c- macrophages in AKI induced renal fibrosis, which are widely considered to be derived from derived from sac yolk. The AKI to CKD transition was induced by severe (30 min) ischemia reperfusion (I/R).
Results
We found CCR2 deficience alleviated acute kidney injury after I/R, which is consistent with previous reports, however, deteriorates renal fibrosis in CKD phase. Furthermore, we identified the cell type in CCR2-/- mice with I/R induced CKD, and it showed Ly6C- macrophages were predominantly infiltrated in CCR2-/- kidney during CKD phase after I/R, which suggested that Ly6C- macrophages play a critical role in AKI induced renal fibrosis. To further confirm the hypothesis, we used chlodronate liposome to deplete the renal Ly6c- macrophages in CCR2-/- mice during I/R induced CKD, and we found renal injury and fibrosis were both alleviated compared to CCR2-/- with PBS intervention. Similar results were identified in wild type mice by depletion of Ly6C- macrophages with chlodronate liposome. Furthermore, Ly6C- macrophages were extracted and adoptive transferred to severe immune deficient mice, which showed that renal injury and fibrosis were directly induced by Ly6C- macrophages. In vitro, we further confirmed that Ly6C- macrophages exerted their profibrotic function by promoting fibroblasts transdifferentiation into myofibroblasts.
Conclusion
In conclusion, kidney Ly6C- macrophages play an important role in directly promoting ischemia induced renal fibrosis, and this function is related to affecting fibroblast transdifferentiation.
Funding
- Government Support - Non-U.S.