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Abstract: PO1709

Deletion of MCP-1 in Podocytes Does Not Protect Against Glomerular Injury

Session Information

Category: Glomerular Diseases

  • 1204 Podocyte Biology

Authors

  • Bondi, Corry D., 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

Over the past three decades, the global burden of chronic kidney disease (CKD) has nearly doubled straining healthcare budgets. Understanding the role of podocytes in the pathophysiology of proteinuric disease is important for development of novel treatments. Prior studies implicate monocyte chemoattractant protein-1 (MCP-1) in podocyte injury, but the source of MCP-1 has not been definitely identified. Both MCP-1 and its cognate receptor, CCR2, are expressed in podocytes. Therefore, using podocyte-specific MCP-1 knockout mice (PODO-MCP-1-/-), we evaluated whether autocrine MCP-1 signaling by podocytes contributes to proteinuric CKD.

Methods

PODO-MCP-1-/- mice were generated by crossing MCP-1 floxed mice with mice harboring Cre recombinase under the control of the podocin promoter. Knockout mice and wild-type littermates were subjected to angiotensin II by osmotic minipumps (Ang II; 1.5mg/kg/day) for 28 days. Weekly spot urines were collected, assessed with ELISA for albuminuria, and results normalized to urinary creatinine. After 28 days, kidneys were harvested and histologic, immunofluorescent, immunoblot, and quantitative PCR analyses were performed. Results are reported as mean ± S.E.M. Threshold for significance was P<.05.

Results

There were no baseline differences in bodyweight, histology, and urinary albumin levels between the two groups. Following 28 days of Ang II infusion, histologic analysis revealed renal pathology particularly glomerulosclerosis. There were no significant differences in bodyweight, albuminuria, renal function, expression of nephrin and WT1, and number of podocytes. Ccr2 gene expression also revealed no significant difference.

Conclusion

Our results demonstrate that podocyte-specific MCP-1 production is not a major contributor to Ang II-induced glomerular injury as demonstrated by lack of protection in the podocyte-specific MCP-1 knockout mice. Future studies will evaluate other sources of MCP-1 that may impact disease.

Funding

  • NIDDK Support