Journal of the American Society of Nephrology
2007 JASN IMPACT FACTOR 7.111 HOME   AUTHOR INFO   EDITORIAL BOARD   SUBSCRIBE   FEEDBACK   ALERTS   HELP 
    advanced
CURRENT ISSUE ARCHIVES JASN Express ONLINE SUBMISSION


This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by MOZES, M. M.
Right arrow Articles by KOPP, J. B.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by MOZES, M. M.
Right arrow Articles by KOPP, J. B.
J Am Soc Nephrol 10:271-280, 1999
© 1999 American Society of Nephrology

REGULAR ARTICLES

Renal Expression of Fibrotic Matrix Proteins and of Transforming Growth Factor-ß (TGF-ß) Isoforms in TGF-ß Transgenic Mice

MIKLOS M. MOZES*,{dagger}, ERWIN P. BÖTTINGER§, TERRY A. JACOT{ddagger} and JEFFREY B. KOPP{dagger}

* Institute of Pathophysiology, Semmelweis University Medical School, Budapest, Hungary
{dagger} Kidney Disease Section, National Institute of Diabetes and Digestive and Kidney, National Institutes of Health, Bethesda, Maryland
{ddagger} Renal Cell Biology Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland
§ Laboratory of Chemoprevention, National Cancer Institute, National Institutes of Health, Bethesda, Maryland

Correspondence to Dr. Jeffrey Kopp, Building 10, Room 3N116, National Institutes of Health, Bethesda, MD 20892-1268. Phone: 301-594-3403; Fax: 301-402-0014; E-mail: jbkopp{at}nih.gov

Abstract. Renal pathology in mice that are transgenic for the murine albumin enhancer/promoter linked to a full-length porcine transforming growth factor-ß1 (TGF-ß1) gene has been described previously. In these mice, transgene expression is limited to the liver and the plasma level of TGF-ß is increased. The earliest renal pathologic change is glomerulosclerosis, at 3 wk of age, and this is followed by tubulointerstitial fibrosis. In this study, it was hypothesized that circulating TGF-ß1 increases renal extracellular matrix accumulation and activates local TGF-ß gene expression. Immunostaining at 5 wk revealed increased amounts of collagen I and III within the mesangium, glomerular capillary loops, and interstitium, while the amount of collagen IV was normal. Similarly, Northern analysis showed increased expression of mRNA encoding collagen I and III, as well as biglycan and decorin, while the expression of collagen IV was unchanged. These changes began as early as 1 wk of age, a time before the appearance of glomerulosclerosis. To evaluate matrix degradation, collagenase IV activity was evaluated by gelatin zymography and an increase in matrix metalloproteinase-2 was found. Finally, the production of tissue inhibitors of metalloproteinase was evaluated. Tissue inhibitor of metalloproteinase-1 (TIMP-1) mRNA was increased 18-fold, while TIMP-2 and TIMP-3 were unchanged. In 2-wk-old transgenic kidney, local expression of TGF-ß1, ß2, and ß3 protein was similar to wild-type mice. In 5-wk-old transgenic mice, TGF-ß1 and ß2 protein was present in increased amounts within glomeruli, and renal TGF-ß1 mRNA was increased threefold. It is concluded that elevated levels of circulating TGF-ß1 may act on the kidney to increase matrix protein production and decrease matrix remodeling. Only after glomerulosclerosis is established does local glomerular overproduction of TGF-ß become manifest.




This article has been cited by other articles:


Home page
 Am. J. Physiol. Renal Physiol.Home page
W.-Z. Ying, K. Aaron, and P. W. Sanders
Mechanism of dietary salt-mediated increase in intravascular production of TGF-{beta}1
Am J Physiol Renal Physiol, August 1, 2008; 295(2): F406 - F414.
[Abstract] [Full Text] [PDF]

Home page
 J. Am. Soc. Nephrol.Home page
R. Tan, J. Zhang, X. Tan, X. Zhang, J. Yang, and Y. Liu
Downregulation of SnoN Expression in Obstructive Nephropathy Is Mediated by an Enhanced Ubiquitin-Dependent Degradation
J. Am. Soc. Nephrol., October 1, 2006; 17(10): 2781 - 2791.
[Abstract] [Full Text] [PDF]

Home page
 J. Pharmacol. Exp. Ther.Home page
J. Bolbrinker, S. Markovic, M. Wehland, W. B. W. H. Melenhorst, H. van Goor, and R. Kreutz
Expression and Response to Angiotensin-Converting Enzyme Inhibition of Matrix Metalloproteinases 2 and 9 in Renal Glomerular Damage in Young Transgenic Rats with Renin-Dependent Hypertension
J. Pharmacol. Exp. Ther., January 1, 2006; 316(1): 8 - 16.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Pathol.Home page
T. Quan, T. He, S. Kang, J. J. Voorhees, and G. J. Fisher
Solar Ultraviolet Irradiation Reduces Collagen in Photoaged Human Skin by Blocking Transforming Growth Factor-{beta} Type II Receptor/Smad Signaling
Am. J. Pathol., September 1, 2004; 165(3): 741 - 751.
[Abstract] [Full Text] [PDF]

Home page
 HypertensionHome page
P. W. Sanders
Salt Intake, Endothelial Cell Signaling, and Progression of Kidney Disease
Hypertension, February 1, 2004; 43(2): 142 - 146.
[Abstract] [Full Text] [PDF]

Home page
 J. Am. Soc. Nephrol.Home page
J. Yang, X. Zhang, Y. Li, and Y. Liu
Downregulation of Smad Transcriptional Corepressors SnoN and Ski in the Fibrotic Kidney: An Amplification Mechanism for TGF-{beta}1 Signaling
J. Am. Soc. Nephrol., December 1, 2003; 14(12): 3167 - 3177.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Renal Physiol.Home page
W.-Z. Ying and P. W. Sanders
The interrelationship between TGF-{beta}1 and nitric oxide is altered in salt-sensitive hypertension
Am J Physiol Renal Physiol, November 1, 2003; 285(5): F902 - F908.
[Abstract] [Full Text] [PDF]

Home page
 J. Am. Soc. Nephrol.Home page
L. Bao, J. Zhou, V. M. Holers, and R. J. Quigg
Excessive Matrix Accumulation in the Kidneys of MRL/lpr Lupus Mice Is Dependent on Complement Activation
J. Am. Soc. Nephrol., October 1, 2003; 14(10): 2516 - 2525.
[Abstract] [Full Text] [PDF]

Home page
 J. Am. Soc. Nephrol.Home page
J.-J. Boffa, Y. Lu, S. Placier, A. Stefanski, J.-C. Dussaule, and C. Chatziantoniou
Regression of Renal Vascular and Glomerular Fibrosis: Role of Angiotensin II Receptor Antagonism and Matrix Metalloproteinases
J. Am. Soc. Nephrol., May 1, 2003; 14(5): 1132 - 1144.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
C. Dai, J. Yang, and Y. Liu
Transforming Growth Factor-beta 1 Potentiates Renal Tubular Epithelial Cell Death by a Mechanism Independent of Smad Signaling
J. Biol. Chem., March 28, 2003; 278(14): 12537 - 12545.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Renal Physiol.Home page
H. W. Schnaper, T. Hayashida, S. C. Hubchak, and A.-C. Poncelet
TGF-beta signal transduction and mesangial cell fibrogenesis
Am J Physiol Renal Physiol, February 1, 2003; 284(2): F243 - F252.
[Abstract] [Full Text] [PDF]

Home page
 Physiol. Rev.Home page
H. Pavenstadt, W. Kriz, and M. Kretzler
Cell Biology of the Glomerular Podocyte
Physiol Rev, January 1, 2003; 83(1): 253 - 307.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Regul. Integr. Comp. Physiol.Home page
A. J. Dahly, K. M. Hoagland, A. K. Flasch, S. Jha, S. R. Ledbetter, and R. J. Roman
Antihypertensive effects of chronic anti-TGF-beta antibody therapy in Dahl S rats
Am J Physiol Regulatory Integrative Comp Physiol, September 1, 2002; 283(3): R757 - R767.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Pathol.Home page
H. Okada, T. Inoue, Y. Kanno, T. Kobayashi, Y. Watanabe, J. B. Kopp, R. M. Carey, and H. Suzuki
Interstitial Fibroblast-Like Cells Express Renin-Angiotensin System Components in a Fibrosing Murine Kidney
Am. J. Pathol., March 1, 2002; 160(3): 765 - 772.
[Abstract] [Full Text] [PDF]

Home page
 J. Am. Soc. Nephrol.Home page
P. J. MARGETTS, M. KOLB, T. GALT, C. M. HOFF, T. R. SHOCKLEY, and J. GAULDIE
Gene Transfer of Transforming Growth Factor-{beta}1 to the Rat Peritoneum: Effects on Membrane Function
J. Am. Soc. Nephrol., October 1, 2001; 12(10): 2029 - 2039.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Renal Physiol.Home page
B. Y. Chin, A. Mohsenin, S. X. Li, A. M. K. Choi, and M. E. Choi
Stimulation of pro-{alpha}1(I) collagen by TGF-{beta}1 in mesangial cells: role of the p38 MAPK pathway
Am J Physiol Renal Physiol, March 1, 2001; 280(3): F495 - F504.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Pathol.Home page
D. Cosgrove, K. Rodgers, D. Meehan, C. Miller, K. Bovard, A. Gilroy, H. Gardner, V. Kotelianski, P. Gotwals, A. Amatucci, et al.
Integrin {alpha}1{beta}1 and Transforming Growth Factor-{beta}1 Play Distinct Roles in Alport Glomerular Pathogenesis and Serve as Dual Targets for Metabolic Therapy
Am. J. Pathol., November 1, 2000; 157(5): 1649 - 1659.
[Abstract] [Full Text] [PDF]

Home page
 J. Gerontol. A Biol. Sci. Med. Sci.Home page
N. Gagliano, B. Arosio, D. Santambrogio, M. R. Balestrieri, G. Padoani, J. Tagliabue, S. Masson, C. Vergani, and G. Annoni
Age-Dependent Expression of Fibrosis-Related Genes and Collagen Deposition in Rat Kidney Cortex
J. Gerontol. A Biol. Sci. Med. Sci., August 1, 2000; 55(8): 365B - 372.
[Abstract] [Full Text]

Home page
 Am. J. Physiol. Renal Physiol.Home page
M. Isono, A. Mogyorosi, D. C. Han, B. B. Hoffman, and F. N. Ziyadeh
Stimulation of TGF-beta type II receptor by high glucose in mouse mesangial cells and in diabetic kidney
Am J Physiol Renal Physiol, May 1, 2000; 278(5): F830 - F838.
[Abstract] [Full Text] [PDF]

Home page
 Nephrol Dial TransplantHome page
A. Mogyorosi and F. N. Ziyadeh
GLUT1 and TGF-{beta}: the link between hyperglycaemia and diabetic nephropathy
Nephrol. Dial. Transplant., December 1, 1999; 14(12): 2827 - 2829.
[Abstract] [Full Text] [PDF]


HOME CURRENT ISSUE ARCHIVES JASN Express ONLINE SUBMISSION AUTHOR INFO
EDITORIAL BOARD SUBSCRIBE FEEDBACK ALERTS HELP

Copyright © 2008 by the American Society of Nephrology. Online ISSN: 1533-3450 Print ISSN: 1046-6673