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Experimental Diabetes Research
Volume 2011 (2011), Article ID 192564, 9 pages
Research Article

NF-κB-Inducing Kinase Increases Renal Tubule Epithelial Inflammation Associated with Diabetes

1Division of Endocrinology and Stark Diabetes Center, Department of Internal Medicine, The University of Texas Medical Branch, 301 University Baulevard, Galveston, TX 77555-1060, USA
2Sealy Center for Molecular Medicine, The University of Texas Medical Branch, Galveston, TX 77555-1060, USA
3Department of Ophthalmology & Visual Sciences, The University of Texas Medical Branch, Galveston, TX 77555-1060, USA

Received 5 May 2011; Accepted 22 June 2011

Academic Editor: Raffaele Marfella

Copyright © 2011 Yanhua Zhao et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


The impact of increased NF-κB-inducing kinase (NIK), a key component of the NF-κB activation pathways, on diabetes-induced renal inflammation remains unknown. We overexpressed NIK wild type (NIKwt) or kinase-dead dominant negative mutants (NIKdn) in HK-2 cells and demonstrated that RelB and p52, but not RelA, abundance and DNA binding increased in nuclei of NIKwt but not NIKdn overexpressed cells, and this corresponded with increases in multiple proinflammatory cytokines. Since TRAF3 negatively regulates NIK expression, we silenced TRAF3 by >50%; this increased nuclear levels of p52 and RelB, and transcript levels of proinflammatory cytokines and transcription factors. In HK-2 cells and mouse primary proximal tubule epithelial cells treated with methylglyoxal-modified albumin, multiple proinflammatory cytokines and NIK were increased in association with increased nuclear RelB and p52. These observations indicate that NIK regulates proinflammatory responses of renal proximal tubular epithelial cells via mechanisms involving TRAF3 and suggest a role for NF-κB noncanonical pathway activation in modulating diabetes-induced inflammation in renal tubular epithelium.