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Kidney Week

Abstract: PO0637

PP2Acα Promotes Macrophage Accumulation and Activation to Accelerate Tubular Cell Death and Kidney Fibrosis Through Regulating Rap1 and TNFα Production

Session Information

  • CKD Mechanisms - 2
    October 22, 2020 | Location: On-Demand
    Abstract Time: 10:00 AM - 12:00 PM

Category: CKD (Non-Dialysis)

  • 2103 CKD (Non-Dialysis): Mechanisms


  • Liang, Yan, Nanjing Medical University, Nanjing, Jiangsu, China
  • Dai, Chunsun, Nanjing Medical University, Nanjing, Jiangsu, China

Macrophage accumulation and activation play an essential role for kidney fibrosis, the underlying mechanisms remain to be explored.


Analyzing the kidneys of patients and animal models with kidney fibrosis. Generating the mice with macrophage PP2Acα ablation.


We observed a significantly increased induction of PP2Acα in macrophages. We then generated mice with macrophage-specific deletion of PP2Acα. These mice developed less renal fibrosis as indicated by less macrophage accumulation, tubular atrophy or extracellular matrix deposition. In cultured cells, the deficiency of PP2Acα in macrophages resulted in decreased cell motility by inhibiting the activity of Rap1. Furthermore, TNFa production was downregulated in macrophages with PP2Acα-deficiency and co-culture of PP2Acα-deficient macrophages and renal tubular cells resulted in less tubular cell death, which was due to decreased TNFα production via phosphorylation of STAT6 in macrophages.


This study shows that PP2A promotes macrophage accumulation and activation, hence accelerating tubular cell death and kidney fibrosis through regulating Rap1 and TNFa production.