Kidney Week

Abstract: TH-PO0324

Single-Cell Transcriptome Sequencing Reveals That Periglomerular Macrophages Aggravate Podocyte Injury in Minimal Change Disease

Session Information

• Glomerular Diseases: Omics
  October 22, 2026 | Location: Exhibit Hall A, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Glomerular Diseases

• 1401 Glomerular Diseases: Mechanisms, including Podocyte Biology

Authors

• Chen, Qilin, Department of Nephrology Children's Hospital of Chongqing Medical University, National Clinical Research Center for Children and Adolescents' Health and Diseases, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Pediatric Metabolism and Inflammatory Disease, Chongqing, China

Qilin Chen, PhD

• Li, Shuying, Department of Nephrology Children's Hospital of Chongqing Medical University, National Clinical Research Center for Children and Adolescents' Health and Diseases, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Pediatric Metabolism and Inflammatory Disease, Chongqing, China

Shuying Li

• Yang, Haiping, Department of Nephrology Children's Hospital of Chongqing Medical University, National Clinical Research Center for Children and Adolescents' Health and Diseases, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Pediatric Metabolism and Inflammatory Disease, Chongqing, China

Haiping Yang

• Qiu, Li, Department of Nephrology Children's Hospital of Chongqing Medical University, National Clinical Research Center for Children and Adolescents' Health and Diseases, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Pediatric Metabolism and Inflammatory Disease, Chongqing, China

Li Qiu

Background

In minimal change disease (MCD), characterized by podocyte injury, renal immune cell infiltration can aggravate the condition into focal segmental glomerulosclerosis (FSGS) with capsular adhesion, though the underlying mechanism remains unclear.

Methods

Single-cell transcriptomic sequencing (scRNA-seq) was performed on kidney biopsy tissues, peripheral blood, and urinary samples from pNS patients with MCD, as well as on enriched Cd11b+ cells isolated from the kidneys and spleens of adriamycin-induced podocyte injury mice (ADR mice). Various animal models, in vivo fluorescence tracing, primary cell co-culture systems, and pathway inhibition experiments were used to systematically explore the interactions and molecular mechanisms among the key cell subsets.

Results

In children with MCD, a subset of parietal epithelial cells (PECs) activated by AP-1-related transcription factors can recruit MNPs to infiltrate the periglomerular region. In ADR mice, periglomerular MNP infiltration positively correlates with glomerulosclerosis.Unlike in other children with massive proteinuria (IgAN), renal MNPs in MCD patients were mainly derived from circulating monocytes, as confirmed by fluorescent tracer mouse experiments. Notably, C1QL1 expression in podocytes near the glomerular capsule wall and its receptor BAI3 in PECs were identified in both patient samples and disease models, potentially mediating podocyte–PEC adhesion. Transwell assays demonstrated that Cd11b+ cells from the kidneys of ADR mice exacerbate podocyte injury and induce C1QL1 expression via CXCL1 and other molecules. Treatment with the AP-1 inhibitor T5224 significantly reduced proteinuria in ADR mice, suppressed inflammatory PEC activation and recruitment, and markedly decreased periglomerular MNP infiltration. Collectively, these findings reveal that in MCD, PECs recruit MNPs to the periglomerular region, which in turn aggravate podocyte injury through CXCL1 and other secreted factors. This process induces podocyte C1QL1 expression, which binds to PEC BAI3, ultimately leading to capsular wall adhesion.

Conclusion

In MCD, AP-1-activated PECs recruit circulating monocyte-derived macrophages to the periglomerular region, where they exacerbate podocyte injury and induce C1QL1 and BAI3-mediated podocyte and PEC adhesion, thereby promoting capsular adhesion and progression to FSGS.