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Abstract: FR-PO731

miR-210-3p Inhibition Prevents Macrophage M2-Like Polarization and Decreases Fibrosis in Murine ADPKD

Session Information

Category: Genetic Diseases of the Kidneys

  • 1001 Genetic Diseases of the Kidneys: Cystic


  • Patil, Ameya P., Medical College of Wisconsin, Wauwatosa, Wisconsin, United States
  • Sweeney, William E., Medical College of Wisconsin, Wauwatosa, Wisconsin, United States
  • Pan, Cynthia G., Medical College of Wisconsin, Wauwatosa, Wisconsin, United States
  • Avner, Ellis D., Medical College of Wisconsin, Wauwatosa, Wisconsin, United States

Autosomal Dominant Polycystic Kidney Disease (ADPKD) is the most common life-threatening hereditary renal disease with an incidence of 1 in 400 to 1 in 1000 individuals. The decline in renal function in ADPKD correlates with the development of renal fibrosis in the peri-cystic local micro-environment (PLM) along withincreased expression of miR-210-3p.A large proportion of the cells in PLM are identified as macrophages (MØs). These MØs undergo a phenotypic switch from M1-like (INOS +) M2-like (arginase +) as fibrosis progresses.


LNA enhanced anti-miR’s(Qiagen) is administered IP from PN14 to PN 28 or PN42 at a dose of 10 um/gm/ Q 4 days. At harvest (PN28 or PN42), one halves of each kidneyis formalin fixed paraffin embedded (FFPE) while the other halves are analyzed by flow cytometry.Serial FFPE sections are analyzed for fibrosis (trichrome staining) and proliferation (PCNA) by Image J software,macrophage phenotyped with IHC or IF.MØphenotypic changes areassessed by flow cytometry and IF or IHC of serial sections. Both wild-type and cystic kidneys are used to obtain MØs, WT-Mac, and C-Mac, respectively, as well as epithelial cells, WTEC and CEC, respectively that were co-cultured in transwells.


In vivo targeting of miR-210-3p with an anti-miR reduces both fibrosis and proliferation in PLM areas and significantly improved renal function at PN42. MØ phenotype assessment of anti-miR-210-3p treated kidneys demonstrates a significant reduction in M2 (from 1900 cells to 1000, p <0.05). Data from co-culture experimentsdemonstrate C-Macs show an increased change to M2, assessed by flow cytometry and express increased levels of Arg1, Mrc1, Egf, Retnla and decreased levels of Tnf transcripts when co-cultured with CEC in comparison to WTEC.


We demonstrate that in vivomiRNA inhibition of miR-210-3p significantly reduced fibrosis by reducing MØ phenotypic change to M2-like. In agreement with published studies miRNAs regulated transcription factors associated with MØ phenotype change to M2. Induction of MØphenotypic change to M2-like by the CEC via miRNA changes within the MØshas not been studied in depth and requires further investigation. miRNAs are an attractive target as these molecules are small in size and exogenously administered anti-miR concentrates in the kidney.


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