Egr-1 deficiency protects from renal inflammation and fibrosis

J Mol Med (Berl). 2016 Aug;94(8):933-42. doi: 10.1007/s00109-016-1403-6. Epub 2016 Mar 9.


NF-κB and TGFβ play critical roles in renal inflammation and fibrosis, and their regulation in the kidney is thus of great interest. Early growth response-1 (Egr-1), a transcription factor belonging to the immediate early gene family, has been found to regulate inflammation and fibrosis in non-kidney tissues, but its role in renal failure has not been clear. In this study, wild-type and Egr1 (-/-) mice were fed with an adenine-enriched diet to induce tubulointerstitial nephritis (TIN), and primary tubular epithelial cells (PTECs) were treated with pro-inflammatory and pro-fibrotic cytokines. Kidney tissues from patients with or without renal failure were stained for Egr-1. Our results showed that Egr-1 expression was upregulated in the kidney with TIN, and the tubular epithelial cell is the primary site for Egr-1 upregulation and nuclear translocation. Egr1 (-/-) mice were protected from renal failure, reflected by low levels of serum urea and creatinine. The protective effect was related to an attenuation of tubular injury, immune cell infiltration, NF-κB activity, and cytokine/chemokine expressions in the kidney. Renal fibrotic area and TGFβ signaling were also reduced in Egr1 (-/-) mice. In vitro study showed that Egr-1 deficiency attenuated the ordinary responses of PTECs to TNFα and TGFβ. Importantly, Egr-1 is of clinical significance since the activity of Egr-1 in renal tubular cells was upregulated in renal failure patients. Our study highlights the integrative role of Egr-1 in renal inflammation and fibrosis. Thus, Egr-1 may serve as a therapeutic target for human kidney diseases.

Key messages: Renal failure activates Egr-1 in human and mouse tubular cells. Egr-1 deficiency attenuates NF-κB and TGFβ-mediated renal inflammation/fibrosis. Egr1 (-/-) PTECs respond weakly to pro-inflammatory or pro-fibrotic stimulation.

Keywords: Early growth response-1; NLRP3 inflammasome; Renal failure; Renal fibrosis; Renal inflammation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cells, Cultured
  • Early Growth Response Protein 1 / genetics*
  • Early Growth Response Protein 1 / metabolism
  • Fibrosis
  • Gene Knockout Techniques
  • Humans
  • Kidney / immunology
  • Kidney / metabolism
  • Kidney / pathology
  • Mice, Inbred C57BL
  • Mice, Knockout
  • NF-kappa B / metabolism
  • NLR Family, Pyrin Domain-Containing 3 Protein / metabolism
  • Nephritis, Interstitial / immunology
  • Nephritis, Interstitial / metabolism*
  • Transforming Growth Factor beta / metabolism


  • Early Growth Response Protein 1
  • Egr1 protein, mouse
  • NF-kappa B
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Nlrp3 protein, mouse
  • Transforming Growth Factor beta