TL1-A can engage death receptor-3 and activate NF-kappa B in endothelial cells

BMC Nephrology

John R Bradley¹  Jordan S Pober³  Hanzhe Liu²  Xinwang Zhu²  Rafia S Al-Lamki¹  Jun Wang² 

[1] Department of Medicine, University of Cambridge, School of Clinical Medicine, Addenbrooke’s Hospital, Box 157, Hills Road, Cambridge CB2 0QQ, UK;Department of nephrology, First Hospital of China Medical University, Nanjing Street, 110001 Shenyang, P.R. China;The Boyer Centre for Molecular Medicine, Yale University School of Medicine, 10 Amistad Street, Room 401D, New Haven, CT 06520, USA

关键词: Inflammation;    Death receptor;    Endothelial cells;    Kidney;   

Others  :  1082573
DOI  :  10.1186/1471-2369-15-178

 received in 2014-04-04, accepted in 2014-10-31,  发布年份 2014

【 摘 要 】

Background

Death receptors (DRs) play an important role in renal pathology. We have shown that DR3 is inducibly expressed on renal tubular epithelial cells in the setting of inflammatory injuries. In this study we investigate the expression of DR3 in renal endothelial cells and their response to TL1A, the only known ligand of DR3.

Methods

We did RT-PCR, flow cytometry and subcellular immunoblotting to examine the expression and function of DR3 in cells in vitro. We did organ culture of human and mouse tissue to examine expression and signal of DR3 in vivo.

Results

DR3 is expressed in some interstitial vascular endothelial cells (EC) in human kidney in situ; these EC also respond to its ligand TL1A by activating NF-κB. Very low levels of DR3 can be detected on the cell surface of cultured human umbilical vein (HUV) EC, which do not respond to TL1A. HUVEC transfected to overexpress DR3 become responsive to TL1A, assessed by IκBα degradation and E-selectin induction, indicating that the signaling components needed for DR3 responsiveness are expressed. TL1A induces NF-κB activation in EC in renal and cardiac tissue from wild type but not DR3 knock-out mice.

Conclusion

TL1A and DR3 activate NF-κB in vascular endothelial cells, and can be an important regulator of renal interstitial vascular injury.

【 授权许可】

   
2014 Wang et al.; licensee BioMed Central Ltd.

【 图 表 】

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