Egr-1 deficiency protects from renal inflammation and fibrosis.
J Mol Med (Berl)
; 94(8): 933-42, 2016 08.
Article
em En
| MEDLINE
| ID: mdl-26960759
ABSTRACT
UNLABELLED NF-κB and TGFß 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 TGFß signaling were also reduced in Egr1 (-/-) mice. In vitro study showed that Egr-1 deficiency attenuated the ordinary responses of PTECs to TNFα and TGFß. 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 TGFß-mediated renal inflammation/fibrosis. Egr1 (-/-) PTECs respond weakly to pro-inflammatory or pro-fibrotic stimulation.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Proteína 1 de Resposta de Crescimento Precoce
/
Nefrite Intersticial
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article