Egr-1 deficiency protects from renal inflammation and fibrosis

Li Chun Ho, Junne Ming Sung, Yi Ting Shen, Huei Fen Jheng, Shun Hua Chen, Pei Jane Tsai, Yau Sheng Tsai

研究成果: Article

31 引文 斯高帕斯(Scopus)

摘要

Abstract: 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.

原文English
頁(從 - 到)933-942
頁數10
期刊Journal of Molecular Medicine
94
發行號8
DOIs
出版狀態Published - 2016 八月 1

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Drug Discovery
  • Genetics(clinical)

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