Nephrol Dial Transplant (2001) 16: 1769-1775
© 2001 European Renal Association-European Dialysis and Transplant Association
Regulation of endothelin-1 and transforming growth factor-ß1 production in cultured proximal tubular cells by albumin and heparan sulphate glycosaminoglycans
1 V Medizinische Klinik, Klinikum Mannheim, University of Heidelberg and 2 Knoll AG, Ludwigshafen, Germany
Background. Both endothelin-1 (ET-1) and transforming growth factor beta 1 (TGF-ß1) have been implicated in the progression of interstitial fibrosis. In the present study we enquired if albumin influences the production of these factors in cultured human proximal tubular epithelial cells (PTEC) and if heparan sulphate glycosaminoglycans (HS-GAG) can inhibit this production.
Methods. ET-1 and TGF-ß1 production in supernatants of PTEC was measured by RIA and ELISA respectively. In addition semi-quantitative reverse transcription polymerase chain reaction (RT-PCR) was performed to study differences in ET-1 and TGF-ß1 mRNA expression. To demonstrate ET-1 or TGF-ß1 binding to heparin or HS-GAG, binding studies by means of dot blot analysis were carried out.
Results. TGF-ß1 and ET-1 were both produced in different concentrations, depending on the PTEC culture tested. Human serum albumin (HSA) up-regulated the production of both factors in a time and dose dependent fashion. The production of these factors was inhibited by heparin under basal and stimulatory conditions. ET-1 production was only inhibited by HS-GAG with a high degree of sulphation. For the inhibition of TGF-ß1 production, the sulphation of HS-GAG was less critical. TGF-ß1, but not ET-1 mRNA expression was inhibited by HS-GAG. Inhibition of sulphation of cell surface HS-GAG resulted in the inhibition of ET-1 but not TGF-ß1 production. Both factors were able to bind to HS-GAG, although this required different amounts of HS-GAG sulphation for each factor.
Conclusions. Our data demonstrate that in PTEC the release of pro-fibrogenic factors can be inhibited by HS-GAG. This may explain to some extent the beneficial effect of heparin in the treatment of interstitial fibrosis.
Keywords: albumin; endothelin-1; heparan sulphate glycosaminoglycans; human proximal tubular epithelial cells; interstitial fibrosis; transforming growth factor ß1
Correspondence and offprint requests to: Dr B. A. Yard, V Medizinische Universitätsklinik, Klinikum Mannheim, University of Heidelberg, Theodor-Kutzer-Ufer 1–3, D-68135 Mannheim, Germany.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  M. M. van Timmeren, M.-L. Gross, W. Hanke, P. A. Klok, H. van Goor, C. A. Stegeman, and S. J. L. Bakker Oleic acid loading does not add to the nephrotoxic effect of albumin in an amphibian and chronic rat model of kidney injury Nephrol. Dial. Transplant., July 24, 2008; (2008) gfn417v1. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G Ferraccioli and G Romano Renal interstitial cells, proteinuria and progression of lupus nephritis: new frontiers for old factors Lupus, June 1, 2008; 17(6): 533 - 540. [Abstract] [PDF]
|
|
|
|
 |
|
 N. Perico, M. Abbate, and G. Remuzzi More on Renal Disease Progression: Is Interstitial Inflammation Truly Protective? J. Am. Soc. Nephrol., June 1, 2007; 18(6): 1630 - 1632. [Full Text] [PDF]
|
|
|
|
 |
|
 R. Diwakar, A. L. Pearson, P. Colville-Nash, N. J. Brunskill, and M. E. C. Dockrell The role played by endocytosis in albumin-induced secretion of TGF-beta1 by proximal tubular epithelial cells Am J Physiol Renal Physiol, May 1, 2007; 292(5): F1464 - F1470. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Caruso-Neves, A. A. S. Pinheiro, H. Cai, J. Souza-Menezes, and W. B. Guggino PKB and megalin determine the survival or death of renal proximal tubule cells PNAS, December 5, 2006; 103(49): 18810 - 18815. [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]
|
|
|
|
 |
|
 J. Prakash, M. Sandovici, V. Saluja, M. Lacombe, R. Q. J. Schaapveld, M. H. de Borst, H. van Goor, R. H. Henning, J. H. Proost, F. Moolenaar, et al. Intracellular Delivery of the p38 Mitogen-Activated Protein Kinase Inhibitor SB202190 [4-(4-Fluorophenyl)-2-(4-hydroxyphenyl)-5-(4-pyridyl)1H-imidazole] in Renal Tubular Cells: A Novel Strategy to Treat Renal Fibrosis J. Pharmacol. Exp. Ther., October 1, 2006; 319(1): 8 - 19. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X. Yu, O. A. Ibrahimi, R. Goetz, F. Zhang, S. I. Davis, H. J. Garringer, R. J. Linhardt, D. M. Ornitz, M. Mohammadi, and K. E. White Analysis of the Biochemical Mechanisms for the Endocrine Actions of Fibroblast Growth Factor-23 Endocrinology, November 1, 2005; 146(11): 4647 - 4656. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Kubo, K. Nakayama, M. Yanai, T. Suzuki, M. Yamaya, M. Watanabe, and H. Sasaki Anticoagulant Therapy for Idiopathic Pulmonary Fibrosis Chest, September 1, 2005; 128(3): 1475 - 1482. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. K. Rangan, Y. Wang, Y.-C. Tay, and D. C.H. Harris Differential effects of albumin on cytokine gene expression in proximal tubular epithelial cells Nephrol. Dial. Transplant., May 1, 2005; 20(5): 1013 - 1014. [Full Text] [PDF]
|
|
|
|
|
|
P. Biswas, A. Roy, R. Gong, A. Yango, E. Tolbert, J. Centracchio, and L. D. Dworkin Hepatocyte growth factor induces an endothelin-mediated decline in glomerular filtration rate Am J Physiol Renal Physiol, January 1, 2005; 288(1): F8 - F15. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. J. Brunskill Albumin Signals the Coming of Age of Proteinuric Nephropathy J. Am. Soc. Nephrol., February 1, 2004; 15(2): 504 - 505. [Full Text] [PDF]
|
|
|
|
|
|
A. Benigni, C. Zoja, D. Corna, C. Zatelli, S. Conti, M. Campana, E. Gagliardini, D. Rottoli, C. Zanchi, M. Abbate, et al. Add-On Anti-TGF-{beta} Antibody to ACE Inhibitor Arrests Progressive Diabetic Nephropathy in the Rat J. Am. Soc. Nephrol., July 1, 2003; 14(7): 1816 - 1824. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Zoja, M. Morigi, and G. Remuzzi Proteinuria and Phenotypic Change of Proximal Tubular Cells J. Am. Soc. Nephrol., June 1, 2003; 14(90001): S36 - 41. [Full Text] [PDF]
|
|
|
|
|
|
C. Zoja, D. Corna, D. Camozzi, D. Cattaneo, D. Rottoli, C. Batani, C. Zanchi, M. Abbate, and G. Remuzzi How To Fully Protect the Kidney in a Severe Model of Progressive Nephropathy: A Multidrug Approach J. Am. Soc. Nephrol., December 1, 2002; 13(12): 2898 - 2908. [Abstract] [Full Text] [PDF]
|
|