Reducing Inflammatory Cytokine Production from Renal Collecting Duct Cells by Inhibiting GATA2 Ameliorates Acute Kidney Injury

Mol Cell Biol. 2017 Oct 27;37(22):e00211-17. doi: 10.1128/MCB.00211-17. Print 2017 Nov 15.


Acute kidney injury (AKI) is a leading cause of chronic kidney disease. Proximal tubules are considered to be the primary origin of pathogenic inflammatory cytokines in AKI. However, it remains unclear whether other cell types, including collecting duct (CD) cells, participate in inflammatory processes. The transcription factor GATA2 is specifically expressed in CD cells and maintains their cellular identity. To explore the pathophysiological function of GATA2 in AKI, we generated renal tubular cell-specific Gata2 deletion (G2CKO) mice and examined their susceptibility to ischemia reperfusion injury (IRI). Notably, G2CKO mice exhibited less severe kidney damage, with reduced granulomacrophagic infiltration upon IRI. Transcriptome analysis revealed that a series of inflammatory cytokine genes were downregulated in GATA2-deficient CD cells, suggesting that GATA2 induces inflammatory cytokine expression in diseased kidney CD cells. Through high-throughput chemical library screening, we identified a potent GATA inhibitor. The chemical reduces cytokine production in CD cells and protects the mouse kidney from IRI. These results revealed a novel pathological mechanism of renal IRI, namely, that CD cells produce inflammatory cytokines and promote IRI progression. In injured kidney CD cells, GATA2 exerts a proinflammatory function by upregulating inflammatory cytokine gene expression. GATA2 can therefore be considered a therapeutic target for AKI.

Keywords: Gata2; acute kidney disease; inflammation; kidney.

MeSH terms

  • Acute Kidney Injury / genetics*
  • Acute Kidney Injury / immunology
  • Animals
  • Cytokines / genetics*
  • Disease Models, Animal
  • GATA2 Transcription Factor / genetics*
  • Gene Expression Profiling
  • Gene Knockout Techniques
  • High-Throughput Screening Assays
  • Kidney Tubules, Collecting / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Reperfusion Injury


  • Cytokines
  • GATA2 Transcription Factor
  • Gata2 protein, mouse