AJP - Renal Journal of Applied Physiology
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Am J Physiol Renal Physiol 277: F766-F772, 1999;
0363-6127/99 $5.00
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
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Guo, G.
Right arrow Articles by Klahr, S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Guo, G.
Right arrow Articles by Klahr, S.
Vol. 277, Issue 5, F766-F772, November 1999

Role of TNFR1 and TNFR2 receptors in tubulointerstitial fibrosis of obstructive nephropathy

Guangjie Guo, Jeremiah Morrissey, Ruth McCracken, Timothy Tolley, and Saulo Klahr

Department of Internal Medicine and the Department of Cell Biology and Physiology, Washington University School of Medicine at Barnes-Jewish Hospital, St. Louis, Missouri 63110-1092

Unilateral ureteral obstruction (UUO) results in tubulointerstitial fibrosis of the obstructed kidney. In this study, we report the contribution of tumor necrosis factor-alpha (TNF-alpha ) to the fibrosis that develops after ureteral obstruction. Mice in which individual TNF-alpha receptors TNFR1 or TNFR2 had been genetically knocked out were used, and results were compared with mice of C57Bl/6 background after 5 days UUO. Both kidneys were removed and examined histologically for changes in interstitial volume (Vvint), collagen IV deposition, alpha -smooth muscle actin (alpha -SMA) matrix score, nuclear factor-kappa B (NF-kappa B) activity, and TNF-alpha mRNA levels. We found that the Vvint of contralateral unobstructed kidneys averaged ~7% and was indistinguishable among the three genotypes of mice. Vvint of ureteral obstructed kidney of C57Bl/6 mice averaged 33 ± 3.9% after 5 days of UUO. Vvint of obstructed kidneys of TNFR1 mice was significantly reduced to 19.4 ± 3.1%, whereas that of TNFR2 mice was significantly decreased to 25.4% ± 4.8%. There was a modest but significant difference between Vvint of TNFR1 and TNFR2 (P < 0.047). Both collagen IV and alpha -SMA matrix scores were decreased significantly in obstructed kidney of TNFR1 mouse compared with that of C57Bl/6 and TNFR2 mice. Nuclear extracts prepared from kidney cortex were found to have a significant increase in NF-kappa B binding activity in obstructed kidney compared with contralateral kidney. Individual knockout of the TNFR1 or TNFR2 genes resulted in significantly less NF-kappa B activation compared with the wild type, with TNFR1 being less than TNFR2 knockout. There was a significant increase in TNF-alpha mRNA in the kidney with ureteral obstruction in all three genotypes. TNFR1 knockout displayed a significant reduction in amount of TNF-alpha mRNA induced compared with wild-type or TNFR2 knockout mice. Treatment of TNFR1 knockout mice with an angiotensin converting enzyme inhibitor further decreased Vvint and TNF-alpha mRNA induction, suggesting an interaction of ANG II and TNF-alpha systems. These results suggest that TNF-alpha contributes, in part, to changes in interstitial volume, myofibroblast differentiation, and NF-kappa B activation in the kidney during ureteral obstruction. These changes appear to be mediated through both TNFR1 and TNFR2 gene products with effects through the TNFR1 receptor predominating. Furthermore, ANG II appears to stimulate TNF-alpha pathophysiological events leading to renal fibrosis.

tumor necrosis factor-alpha ; chronic renal disease; myofibroblasts


This article has been cited by other articles:


Home page
 Am. J. Physiol. Endocrinol. Metab.Home page
P. D. Metcalfe, J. A. Leslie, M. T. Campbell, D. R. Meldrum, K. L. Hile, and K. K. Meldrum
Testosterone exacerbates obstructive renal injury by stimulating TNF-{alpha} production and increasing proapoptotic and profibrotic signaling
Am J Physiol Endocrinol Metab, February 1, 2008; 294(2): E435 - E443.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Regul. Integr. Comp. Physiol.Home page
K. K. Meldrum, R. Misseri, P. Metcalfe, C. A. Dinarello, K. L. Hile, and D. R. Meldrum
TNF-{alpha} neutralization ameliorates obstruction-induced renal fibrosis and dysfunction
Am J Physiol Regulatory Integrative Comp Physiol, April 1, 2007; 292(4): R1456 - R1464.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Renal Physiol.Home page
N. G. Docherty, O. E. O'Sullivan, D. A. Healy, J. M. Fitzpatrick, and R. W. G. Watson
Evidence that inhibition of tubular cell apoptosis protects against renal damage and development of fibrosis following ureteric obstruction
Am J Physiol Renal Physiol, January 1, 2006; 290(1): F4 - F13.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Renal Physiol.Home page
C. Chatziantoniou and J.-C. Dussaule
Insights into the mechanisms of renal fibrosis: is it possible to achieve regression?
Am J Physiol Renal Physiol, August 1, 2005; 289(2): F227 - F234.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Renal Physiol.Home page
R. Misseri, D. R. Meldrum, C. A. Dinarello, P. Dagher, K. L. Hile, R. C. Rink, and K. K. Meldrum
TNF-{alpha} mediates obstruction-induced renal tubular cell apoptosis and proapoptotic signaling
Am J Physiol Renal Physiol, February 1, 2005; 288(2): F406 - F411.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Renal Physiol.Home page
G. Ramesh and W. B. Reeves
TNFR2-mediated apoptosis and necrosis in cisplatin-induced acute renal failure
Am J Physiol Renal Physiol, October 1, 2003; 285(4): F610 - F618.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Renal Physiol.Home page
K. Tsuruya, M. Tokumoto, T. Ninomiya, M. Hirakawa, K. Masutani, M. Taniguchi, K. Fukuda, H. Kanai, H. Hirakata, and M. Iida
Antioxidant ameliorates cisplatin-induced renal tubular cell death through inhibition of death receptor-mediated pathways
Am J Physiol Renal Physiol, August 1, 2003; 285(2): F208 - F218.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Renal Physiol.Home page
S. Klahr and J. Morrissey
Obstructive nephropathy and renal fibrosis
Am J Physiol Renal Physiol, November 1, 2002; 283(5): F861 - F875.
[Abstract] [Full Text] [PDF]

Home page
 J. Am. Soc. Nephrol.Home page
J. Morrissey, G. Guo, K. Moridaira, M. Fitzgerald, R. McCracken, T. Tolley, and S. Klahr
Transforming Growth Factor-{beta} Induces Renal Epithelial Jagged-1 Expression in Fibrotic Disease
J. Am. Soc. Nephrol., June 1, 2002; 13(6): 1499 - 1508.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Renal Physiol.Home page
G. Guo, J. Morrissey, R. McCracken, T. Tolley, H. Liapis, and S. Klahr
Contributions of angiotensin II and tumor necrosis factor-{alpha} to the development of renal fibrosis
Am J Physiol Renal Physiol, May 1, 2001; 280(5): F777 - F785.
[Abstract] [Full Text] [PDF]

Home page
 J. Am. Soc. Nephrol.Home page
J. MORRISSEY, G. GUO, R. MCCRACKEN, T. TOLLEY, and S. KLAHR
Induction of CD14 in Tubular Epithelial Cells During Kidney Disease
J. Am. Soc. Nephrol., September 1, 2000; 11(9): 1681 - 1690.
[Abstract] [Full Text]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Visit Other APS Journals Online