Nephron Experimental Nephrology
Original Paper
Reducing Serum Uric Acid Attenuates TGF-β1-Induced Profibrogenic Progression in Type 2 Diabetic NephropathyKim S.-M.a · Choi Y.-W.a · Seok H.-Y.a · Jeong K.-H.c · Lee S.-H.a · Lee T.-W.c · Ihm C.-G.c · Lim S.J.b · Moon J.-Y.aaDivision of Nephrology, Department of Internal Medicine, and bDepartment of Pathology, Kyung Hee University Hospital at Gangdong, College of Medicine, and cDivision of Nephrology, Department of Internal Medicine, Kyung Hee University, Seoul, Korea
|
|
Log in to MyKarger to check if you already have access to this content.
KAB
Buy a Karger Article Bundle (KAB) and profit from a discount!
If you would like to redeem your KAB credit, please log in.
Save over 20% compared to the individual article price.
Subscribe
For eJournal Archive and eJournal Backfiles information please contact Karger service
Article / Publication Details
Received: March 27, 2012
Accepted: September 08, 2012
Published online: January 09, 2013
Issue release date: February 2013
Number of Print Pages: 13
Number of Figures: 8
Number of Tables: 1
eISSN: 1660-2129 (Online)
For additional information: https://www.karger.com/NEE
Abstract
Background: The pivotal role of transforming growth factor-β1 (TGF-β1)-induced tubulointerstitial fibrosis in the progression of chronic kidney disease is an active topic of research. Recent evidence indicates that hyperuricemia is associated with increased TGF-β1 and progressive tubulointerstitial injury. We examined the hypothesis that lowering serum uric acid attenuates TGF-β1-induced profibrogenic tubular change in type 2 diabetic nephropathy. Methods: KK-Ay/Ta mice, an animal model of type 2 diabetes, were provided access to either regular drinking water or drinking water containing 10 mg/dl of allopurinol. Normal rat kidney epithelial cells were cultured and stimulated with 5 m
© 2013 S. Karger AG, Basel
References
- Johnson RJ, Kang DH, Feig D, Kivlighn S, Kanellis J, Watanabe S, Tuttle KR, Rodriguez-Iturbe B, Herrera-Acosta J, Mazzali M: Is there a pathogenetic role for uric acid in hypertension and cardiovascular and renal disease? Hypertension 2003;41:1183–1190.
- Johnson RJ, Kivlighn SD, Kim YG, Suga S, Fogo AB: Reappraisal of the pathogenesis and consequences of hyperuricemia in hypertension, cardiovascular disease, and renal disease. Am J Kidney Dis 1999;33:225–234.
- Kosugi T, Nakayama T, Heinig M, Zhang L, Yuzawa Y, Sanchez-Lozada LG, Roncal C, Johnson RJ, Nakagawa T: Effect of lowering uric acid on renal disease in the type 2 diabetic db/db mice. Am J Physiol Renal Physiol 2009;297:F481–F488.
- Rao GN, Corson MA, Berk BC: Uric acid stimulates vascular smooth muscle cell proliferation by increasing platelet-derived growth factor A-chain expression. J Biol Chem 1991;266:8604–8608.
- Kanellis J, Watanabe S, Li JH, Kang DH, Li P, Nakagawa T, Wamsley A, Sheikh-Hamad D, Lan HY, Feng L, Johnson RJ: Uric acid stimulates monocyte chemoattractant protein-1 production in vascular smooth muscle cells via mitogen-activated protein kinase and cyclooxygenase-2. Hypertension 2003;41:1287–1293.
- Farquharson CA, Butler R, Hill A, Belch JJ, Struthers AD: Allopurinol improves endothelial dysfunction in chronic heart failure. Circulation 2002;106:221–226.
- Doehner W, Schoene N, Rauchhaus M, Leyva-Leon F, Pavitt DV, Reaveley DA, Schuler G, Coats AJ, Anker SD, Hambrecht R: Effects of xanthine oxidase inhibition with allopurinol on endothelial function and peripheral blood flow in hyperuricemic patients with chronic heart failure: results from two placebo-controlled studies. Circulation 2002;105:2619–2624.
- Butler R, Morris AD, Belch JJ, Hill A, Struthers AD: Allopurinol normalizes endothelial dysfunction in type 2 diabetics with mild hypertension. Hypertension 2000;35:746–751.
- Li JH, Zhu HJ, Huang XR, Lai KN, Johnson RJ, Lan HY: Smad7 inhibits fibrotic effect of TGF-β on renal tubular epithelial cells by blocking Smad2 activation. J Am Soc Nephrol 2002;13:1464–1472.
- Ng YY, Huang TP, Yang WC, Chen ZP, Yang AH, Mu W, Nikolic-Paterson DJ, Atkins RC, Lan HY: Tubular epithelial-myofibroblast transdifferentiation in progressive tubulointerstitial fibrosis in 5/6 nephrectomized rats. Kidney Int 1998;54:864–876.
- Okada H, Danoff TM, Kalluri R, Neilson EG: Early role of Fsp1 in epithelial-mesenchymal transformation. Am J Physiol 1997;273: F563–F574.
- Zavadil J, Bottinger EP: TGF-β and epithelial-to-mesenchymal transitions. Oncogene 2005;24:5764–5774.
- Ito T, Tanimoto M, Yamada K, Kaneko S, Matsumoto M, Obayashi K, Hagiwara S, Murakoshi M, Aoki T, Wakabayashi M, Gohda T, Funabiki K, Maeda K, Horikoshi S, Tomino Y: Glomerular changes in the KK-Ay/Ta mouse: a possible model for human type 2 diabetic nephropathy. Nephrology (Carlton) 2006;11:29–35.
-
Moon JY, Tanimoto M, Gohda T, Hagiwara S, Yamazaki T, Ohara I, Murakoshi M, Aoki T, Ishikawa Y, Lee SH, Jeong KH, Lee TW, Ihm CG, Lim SJ, Tomino Y: Attenuating effect of angiotensin-(1–7) on angiotensin ii-mediated NAD(P)H oxidase activation in type 2 diabetic nephropathy of KK-Ay/Ta mice. Am J Physiol Renal Physiol;300:F1271–F1282.
- Katz A, Caramori ML, Sisson-Ross S, Groppoli T, Basgen JM, Mauer M: An increase in the cell component of the cortical interstitium antedates interstitial fibrosis in type 1 diabetic patients. Kidney Int 2002;61:2058–2066.
- Yang J, Liu Y: Blockage of tubular epithelial to myofibroblast transition by hepatocyte growth factor prevents renal interstitial fibrosis. J Am Soc Nephrol 2002;13:96–107.
- Zeisberg M, Hanai J, Sugimoto H, Mammoto T, Charytan D, Strutz F, Kalluri R: BMP-7 counteracts TGF-β1-induced epithelial-to-mesenchymal transition and reverses chronic renal injury. Nat Med 2003;9:964–968.
- Yang J, Dai C, Liu Y: Hepatocyte growth factor gene therapy and angiotensin II blockade synergistically attenuate renal interstitial fibrosis in mice. J Am Soc Nephrol 2002;13:2464–2477.
- Nagatoya K, Moriyama T, Kawada N, Takeji M, Oseto S, Murozono T, Ando A, Imai E, Hori M: Y-27632 prevents tubulointerstitial fibrosis in mouse kidneys with unilateral ureteral obstruction. Kidney Int 2002;61:1684–1695.
- Li Y, Yang J, Dai C, Wu C, Liu Y: Role for integrin-linked kinase in mediating tubular epithelial to mesenchymal transition and renal interstitial fibrogenesis. J Clin Invest 2003;112:503–516.
- Kang DH, Nakagawa T, Feng L, Watanabe S, Han L, Mazzali M, Truong L, Harris R, Johnson RJ: A role for uric acid in the progression of renal disease. J Am Soc Nephrol 2002;13:2888–2897.
- Humphreys BD, Lin SL, Kobayashi A, Hudson TE, Nowlin BT, Bonventre JV, Valerius MT, McMahon AP, Duffield JS: Fate tracing reveals the pericyte and not epithelial origin of myofibroblasts in kidney fibrosis. Am J Pathol 2010;176:85–97.
- Arias AM: Epithelial mesenchymal interactions in cancer and development. Cell 2001;105:425–431.
- Tepass U, Truong K, Godt D, Ikura M, Peifer M: Cadherins in embryonic and neural morphogenesis. Nat Rev Mol Cell Biol 2000;1:91–100.
- Vanderburg CR, Hay ED: E-cadherin transforms embryonic corneal fibroblasts to stratified epithelium with desmosomes. Acta Anat (Basel) 1996;157:87–104.
- Leyva F, Anker SD, Godsland IF, Teixeira M, Hellewell PG, Kox WJ, Poole-Wilson PA, Coats AJ: Uric acid in chronic heart failure: a marker of chronic inflammation. Eur Heart J 1998;19:1814–1822.
- Doehner W, Springer J, Landmesser U, Struthers AD, Anker SD: Uric acid in chronic heart failure – current pathophysiological concepts. Eur J Heart Fail 2008;10:1269–1270.
- Watanabe S, Kang DH, Feng L, Nakagawa T, Kanellis J, Lan H, Mazzali M, Johnson RJ: Uric acid, hominoid evolution, and the pathogenesis of salt-sensitivity. Hypertension 2002;40:355–360.
- Desco MC, Asensi M, Marquez R, Martinez-Valls J, Vento M, Pallardo FV, Sastre J, Vina J: Xanthine oxidase is involved in free radical production in type 1 diabetes: protection by allopurinol. Diabetes 2002;51:1118–1124.
- Matsumoto S, Koshiishi I, Inoguchi T, Nawata H, Utsumi H: Confirmation of superoxide generation via xanthine oxidase in streptozotocin-induced diabetic mice. Free Radic Res 2003;37:767–772.
- Malik UZ, Hundley NJ, Romero G, Radi R, Freeman BA, Tarpey MM, Kelley EE: Febuxostat inhibition of endothelial-bound XO: Implications for targeting vascular ROS production. Free Radic Biol Med 2011;51:179–184.
Article / Publication Details
Received: March 27, 2012
Accepted: September 08, 2012
Published online: January 09, 2013
Issue release date: February 2013
Number of Print Pages: 13
Number of Figures: 8
Number of Tables: 1
eISSN: 1660-2129 (Online)
For additional information: https://www.karger.com/NEE
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
Get Permission
PubMed ID
