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Abstract: SA-PO1010

Podocyte-Specific Deletion of MCP-1 Fails to Protect Against Angiotensin II- or Adriamycin-Induced Nephropathy

Session Information

Category: Glomerular Diseases

  • 1403 Podocyte Biology

Authors

  • Bondi, Corry D., University of Pittsburgh Department of Medicine, Pittsburgh, Pennsylvania, United States
  • Hartman, Hannah L., University of Pittsburgh Department of Medicine, Pittsburgh, Pennsylvania, United States
  • Rush, Brittney M., University of Pittsburgh Department of Medicine, Pittsburgh, Pennsylvania, United States
  • Tan, Roderick J., University of Pittsburgh Department of Medicine, Pittsburgh, Pennsylvania, United States
Background

Investigating the role of podocytes in the pathophysiology of proteinuric disease is important to remedy the increasing global burden of chronic kidney disease (CKD). Monocyte chemoattractant protein-1 (MCP-1 or CCL2) is a chemokine upregulated in proteinuric CKD. Since podocytes can express both MCP-1 and its receptor (CCR2), we hypothesized that an autocrine MCP-1/CCR2 loop contributes to proteinuric CKD. To test this hypothesis, we generated podocyte-specific MCP-1 knockout mice (Podo-Mcp-1fl/fl) and exposed them to proteinuric injuries.

Methods

Podo-Mcp-1fl/fl mice were generated by crossing MCP-1 floxed mice with mice harboring Cre recombinase under the transcriptional control of the podocin promoter. Podo-Mcp-1fl/fl mice and control littermates were subjected to either angiotensin II (Ang II; 1.5mg/kg/day x 28 days) or Adriamycin (Adr; 18mg/kg) to induce glomerular injury. Weekly spot urines were assessed for albuminuria. After 28 days, sera were collected to assess renal function while kidney tissues were used for histological, immunofluorescence, immunoblot, and quantitative PCR analyses. Unpaired Student’s t-test (two-tailed) was performed for two group comparisons. Log-rank test was used to compare survival distributions. The threshold for significance was P<0.05.

Results

At baseline, there were no between-group differences in body weight, histology, albuminuria, and podocyte markers. After 28 days of injury with either Ang II or Adr, there were no between-group differences in survival, albuminuria, renal function, inflammatory mediators, histopathology, podocyte loss, nephrin expression, and fibrosis.

Conclusion

Due to the lack of protection in the knock-out mice, our findings suggest that podocyte-specific MCP-1 production is not a major contributor to either Ang II- or Adr-induced glomerular injury. MCP-1 signaling must originate from a non-podocyte cell type. Future studies will determine the source cell of MCP-1.

Funding

  • NIDDK Support