NDT Advance Access originally published online on July 27, 2004
Nephrology Dialysis Transplantation 2004 19(10):2505-2512; doi:10.1093/ndt/gfh207
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Nephrol Dial Transplant Vol. 19 No. 10 © ERA-EDTA 2004; all rights reserved
Original Article
NF-
B activation and overexpression of regulated genes in human diabetic nephropathy
1 Division of Nephrology, School of Medicine, Universidad Austral, Valdivia, Chile and 2 Fundación Jiménez Díaz, Universidad Autónoma, Madrid, Spain
Correspondence and offprint requests to: Sergio Mezzano, MD, Department of Nephrology, School of Medicine, Universidad Austral Bueras 1003 2 P, PO Box 8-D, Valdivia, Chile. Email: smezzano{at}uach.cl
Background. Nuclear factor-
B (NF-B) regulates genes involved in renal disease progression, such as the chemokines monocyte chemoattractant protein-1 (MCP-1) and RANTES. NF-B is activated in experimental models of renal injury, and in vitro studies also suggest that proteinuria and angiotensin II could be important NF-B activators. It has been proposed that locally produced MCP-1 may be involved in the development of diabetic nephropathy (DN). We examined the hypothesis that NF-B could be an indicator of renal damage progression in DN.
Methods. Biopsy specimens from 11 patients with type 2 diabeties and overt nephropathy were studied by southwestern histochemistry for the in situ detection of activated NF-B. In addition, by immunohistochemistry and/or in situ hybridization, we studied the expression of MCP-1 and RANTES, whose genes are regulated by NF-B.
Results. NF-B was detected mainly in cortical tubular epithelial cells and, to a lesser extent, in some glomerular and interstitial cells. A strong upregulation of MCP-1 and RANTES was observed in all the cases, mainly in tubular cells, and there was a strong correlation between the expression of these chemokines and NF-B activation in the same cells, as observed in serial sections (r = 0.7; P = 0.01). In addition, the tubular expression of these chemokines was correlated mainly with the magnitude of the proteinuria (P = 0.002) and with interstitial cell infiltration (P<0.05).
Conclusions. The activation of NF-B and the transcription of certain pro-inflammatory chemokines in tubular epithelial cells are markers of progressive DN. Proteinuria might be one of the main factors inducing the observed pro-inflammatory phenotype.
Keywords: diabetic nephropathy; MCP-1; NF-B; RANTES; renal disease progression
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  K. J. Kelly, J. L. Burford, and J. H. Dominguez Postischemic inflammatory syndrome: a critical mechanism of progression in diabetic nephropathy Am J Physiol Renal Physiol, October 1, 2009; 297(4): F923 - F931. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Y. Lee, C. H. Chung, C. C. Khoury, T. K. Yeo, P. E. Pyagay, A. Wang, and S. Chen The monocyte chemoattractant protein-1/CCR2 loop, inducible by TGF-{beta}, increases podocyte motility and albumin permeability Am J Physiol Renal Physiol, July 1, 2009; 297(1): F85 - F94. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Sanchez-Lopez, S. Rayego, R. Rodrigues-Diez, J. S. Rodriguez, R. Rodrigues-Diez, J. Rodriguez-Vita, G. Carvajal, L. S. Aroeira, R. Selgas, S. A. Mezzano, et al. CTGF Promotes Inflammatory Cell Infiltration of the Renal Interstitium by Activating NF-{kappa}B J. Am. Soc. Nephrol., July 1, 2009; 20(7): 1513 - 1526. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. J. Ko, Y. S. Kang, S. Y. Han, M. H. Lee, H. K. Song, K. H. Han, H. K. Kim, J. Y. Han, and D. R. Cha Pioglitazone attenuates diabetic nephropathy through an anti-inflammatory mechanism in type 2 diabetic rats Nephrol. Dial. Transplant., September 1, 2008; 23(9): 2750 - 2760. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Zheng, R. Sinniah, and S. I-H. Hsu Pathogenic Role of NF-{kappa}B Activation in Tubulointerstitial Inflammatory Lesions in Human Lupus Nephritis J. Histochem. Cytochem., May 1, 2008; 56(5): 517 - 529. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. P. Wolkow, M. A. Niewczas, B. Perkins, L. H. Ficociello, B. Lipinski, J. H. Warram, and A. S. Krolewski Association of Urinary Inflammatory Markers and Renal Decline in Microalbuminuric Type 1 Diabetics J. Am. Soc. Nephrol., April 1, 2008; 19(4): 789 - 797. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. F. Navarro-Gonzalez and C. Mora-Fernandez The Role of Inflammatory Cytokines in Diabetic Nephropathy J. Am. Soc. Nephrol., March 1, 2008; 19(3): 433 - 442. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Segerer, R. Djafarzadeh, H.-J. Grone, C. Weingart, D. Kerjaschki, C. Weber, A. J. Kungl, H. Regele, A. E.I. Proudfoot, and P. J. Nelson Selective Binding and Presentation of CCL5 by Discrete Tissue Microenvironments during Renal Inflammation J. Am. Soc. Nephrol., June 1, 2007; 18(6): 1835 - 1844. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. K. Fujihara, G. R. Antunes, A. L. Mattar, D. M. A. C. Malheiros, J. M. Vieira Jr., and R. Zatz Chronic inhibition of nuclear factor-{kappa}B attenuates renal injury in the 5/6 renal ablation model Am J Physiol Renal Physiol, January 1, 2007; 292(1): F92 - F99. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y.-R. Lee, M.-T. Liu, H.-Y. Lei, C.-C. Liu, J.-M. Wu, Y.-C. Tung, Y.-S. Lin, T.-M. Yeh, S.-H. Chen, and H.-S. Liu MCP-1, a highly expressed chemokine in dengue haemorrhagic fever/dengue shock syndrome patients, may cause permeability change, possibly through reduced tight junctions of vascular endothelium cells J. Gen. Virol., December 1, 2006; 87(12): 3623 - 3630. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Schmid, A. Boucherot, Y. Yasuda, A. Henger, B. Brunner, F. Eichinger, A. Nitsche, E. Kiss, M. Bleich, H.-J. Grone, et al. Modular Activation of Nuclear Factor-{kappa}B Transcriptional Programs in Human Diabetic Nephropathy Diabetes, November 1, 2006; 55(11): 2993 - 3003. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Abbate, C. Zoja, and G. Remuzzi How Does Proteinuria Cause Progressive Renal Damage? J. Am. Soc. Nephrol., November 1, 2006; 17(11): 2974 - 2984. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Samikkannu, J. J. Thomas, G. J. Bhat, V. Wittman, and T. J. Thekkumkara Acute effect of high glucose on long-term cell growth: a role for transient glucose increase in proximal tubule cell injury Am J Physiol Renal Physiol, July 1, 2006; 291(1): F162 - F175. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. K. Fujihara, C. R. Sena, D. M. A. C. Malheiros, A. L. Mattar, and R. Zatz Short-term nitric oxide inhibition induces progressive nephropathy after regression of initial renal injury Am J Physiol Renal Physiol, March 1, 2006; 290(3): F632 - F640. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Ruiz-Ortega, M. Ruperez, V. Esteban, J. Rodriguez-Vita, E. Sanchez-Lopez, G. Carvajal, and J. Egido Angiotensin II: a key factor in the inflammatory and fibrotic response in kidney diseases Nephrol. Dial. Transplant., January 1, 2006; 21(1): 16 - 20. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. G. Ewens, R. A. George, K. Sharma, F. N. Ziyadeh, and R. S. Spielman Assessment of 115 Candidate Genes for Diabetic Nephropathy by Transmission/Disequilibrium Test Diabetes, November 1, 2005; 54(11): 3305 - 3318. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. F. Navarro, C. Mora, M. Muros, and J. Garcia Additive Antiproteinuric Effect of Pentoxifylline in Patients with Type 2 Diabetes under Angiotensin II Receptor Blockade: A Short-Term, Randomized, Controlled Trial J. Am. Soc. Nephrol., July 1, 2005; 16(7): 2119 - 2126. [Abstract] [Full Text] [PDF]
|
|