Details

Autor(en) / Beteiligte

• Chen, Qilin
• Jiang, Yaru
• Zhong, Jinjie
• Feng, Xiaoqian
• Jiang, Huimin
• Wan, Junli
• Peng, Liping
• Wang, Mo
• Yang, Haiping
• LI, Qiu

Titel

6693 INCREASED INFILTRATION OF LRG1+VCAN+LY6CHIGH MACROPHAGES ARE ESSENTIAL CONTRIBUTORS TO KIDNEY INJURY IN ADR MICE

Ist Teil von

• Nephrology, dialysis, transplantation, 2023-06, Vol.38 (Supplement_1)

Erscheinungsjahr

2023

Quelle

Oxford Journals 2020 Medicine

Beschreibungen/Notizen

• Abstract Background and Aims The ADR mouse model is a well-established rodent model of FSGS that can manifest with albuminuria. Resident macrophages are present in the tubulointerstitium of the kidney, and circulating macrophages can be recruited to the kidney in disease states. However, the presence of macrophages in glomeruli and the role of macrophages in podocyte injury in ADR mouse models remain unknown. Method Single-cell RNA sequencing comprehensively characterized the expression of macrophages in mice glomeruli. Eight-week-old male BALB/c mice were used to induce ADR model. Immunofluorescence was used to detect the changes of renal macrophages after injected with ADR at different time points. Transwell co-culture system were used to detect the effect of Lrg1+Vcan+Ly6Chigh macrophages on MPCs. HCH6-1,the FPR1 inhibitor were used to restrain ANXA1-FPR1 pathway. Results Totally 506 macrophages were sequenced and Lrg1+Vcan+Ly6Chigh macrophages were significantly increased in ADR induced nephrotic mice glomeruli (P<0.01). The ligand receptor relationship between podocytes and macrophages were changed(P<0.01, means>1). Immunofluorescence demonstrated that macrophages are present in ADR glomeruli(P<0.05). However, the temporal and spatial changes of macrophages in ADR glomeruli still need to be proved by further experiments. After co-culture of Lrg1+Vcan+Ly6Chighmacrophages and MPCs, the expression of nephrin in MPCs decreased(P<0.05), which proved that macrophages can cause podocyte injury. In ADR group, the ANXA1-FPR1 signaling pathway was activated, and renal Lrg1+Vcan+Ly6Chighmacrophage infiltration, albuminuria and renal injury were reduced in ADR+HCH6-1gruop (all P<0.05). Conclusion Lrg1+Vcan+Ly6Chighmacrophages are recruited into mice glomeruli by activation of ANXA1-FPR1 signaling pathway and cause the damage of podocyte.