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 Full Text Full Text (PDF) All Versions of this Article: ASN.2004121070v1 16/5/1371    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Wang, W. Articles by Lan, H. Y. Search for Related Content PubMed PubMed Citation Articles by Wang, W. Articles by Lan, H. Y.

Signaling Mechanism of TGF-1 in Prevention of Renal Inflammation: Role of Smad7

Wansheng Wang^*, Xiao R. Huang^*, Allen G. Li, Fang Liu^*, Jin-Hua Li^*, Luan D. Truong^*,, Xiao J. Wang and Hui Y. Lan^*

^* Departments of Medicine and Pathology, Baylor College of Medicine, Houston, Texas; Department of Dermatology, Oregon Health & Science University, Portland, Oregon; and Department of Pathology, The Methodist Hospital, Houston, Texas

Address correspondence to: Dr. Hui Y. Lan, Department of Medicine-Nephrology, Baylor College of Medicine, One Baylor Plaza, Alkek N520, Houston, TX 77030. Phone: 713-798-1303; Fax: 713-798-5010; hlan{at}bcm.tmc.edu

Received for publication December 10, 2004. Accepted for publication February 16, 2005.

TGF- has been shown to play a critical role in anti-inflammation; however, the signaling mechanisms of TGF- in anti-inflammatory response remains largely unclear. This study reported that mice that overexpress latent TGF-1 on skin are protected against renal inflammation in a model of obstructive kidney disease and investigated the signaling mechanism of TGF-1 in inhibition of renal inflammation in vivo and in vitro. Seven days after urinary obstruction, wild-type mice developed severe renal inflammation, including massive T cell and macrophage infiltration and marked upregulation of IL-1, TNF-, and intercellular adhesion molecule-1 (all P < 0.001). Surprising, renal inflammation was prevented in transgenic mice. This was associated with an increase in latent TGF-1 in circulation (a 10-fold increase) and renal tissues (a 2.5-fold increase). Further studies showed that inhibition of renal inflammation in TGF-1 transgenic mice was also associated with a marked upregulation of renal Smad7 and IB and a suppression of NF-B activation in the diseased kidney (all P < 0.01). These in vivo findings suggested the importance of TGF-–NF-B cross-talk signaling pathway in regulating renal inflammation. This was tested in vitro in a doxycycline-regulated Smad7-expressing renal tubular cell line. Overexpression of Smad7 was able to upregulate IB directly in a time- and dose-dependent manner, thereby inhibiting NF-B activation and NF-B–driven inflammatory response. In conclusion, latent TGF- may have protective roles in renal inflammation. Smad7-mediated inhibition of NF-B activation via the induction of IkB may be the central mechanism by which latent TGF- prevents renal inflammation.

This article has been cited by other articles:

				A. C. K. Chung, X. R. Huang, L. Zhou, R. Heuchel, K. N. Lai, and H. Y. Lan Disruption of the Smad7 gene promotes renal fibrosis and inflammation in unilateral ureteral obstruction (UUO) in mice Nephrol. Dial. Transplant., December 18, 2008; (2008) gfn699v1. [Abstract] [Full Text] [PDF]

				X. R. Huang, A. C. K. Chung, X. J. Wang, K. N. Lai, and H. Y. Lan Mice overexpressing latent TGF-{beta}1 are protected against renal fibrosis in obstructive kidney disease Am J Physiol Renal Physiol, July 1, 2008; 295(1): F118 - F127. [Abstract] [Full Text] [PDF]

				X. R. Huang, A. C.K. Chung, L. Zhou, X. J. Wang, and H. Y. Lan Latent TGF-{beta}1 Protects Against Crescentic Glomerulonephritis J. Am. Soc. Nephrol., February 1, 2008; 19(2): 233 - 242. [Abstract] [Full Text] [PDF]

				S. Hong, C. Lee, and S.-J. Kim Smad7 Sensitizes Tumor Necrosis Factor Induced Apoptosis through the Inhibition of Antiapoptotic Gene Expression by Suppressing Activation of the Nuclear Factor-{kappa}B Pathway Cancer Res., October 1, 2007; 67(19): 9577 - 9583. [Abstract] [Full Text] [PDF]

				H. Guo, J. C.K. Leung, M. F. Lam, L. Y.Y. Chan, A. W.L. Tsang, H. Y. Lan, and K. N. Lai Smad7 Transgene Attenuates Peritoneal Fibrosis in Uremic Rats Treated with Peritoneal Dialysis J. Am. Soc. Nephrol., October 1, 2007; 18(10): 2689 - 2703. [Abstract] [Full Text] [PDF]

				W. Wang, L. Soltero, P. Zhang, X. R. Huang, H. Y. Lan, and H. J. Adrogue Renal inflammation is modulated by potassium in chronic kidney disease: possible role of Smad7 Am J Physiol Renal Physiol, October 1, 2007; 293(4): F1123 - F1130. [Abstract] [Full Text] [PDF]

				S.-M. Ka, X.-R. Huang, H.-Y. Lan, P.-Y. Tsai, S.-M. Yang, H.-A. Shui, and A. Chen Smad7 Gene Therapy Ameliorates an Autoimmune Crescentic Glomerulonephritis in Mice J. Am. Soc. Nephrol., June 1, 2007; 18(6): 1777 - 1788. [Abstract] [Full Text] [PDF]

				Y. Ozawa, H. Kobori, Y. Suzaki, and L. G. Navar Sustained renal interstitial macrophage infiltration following chronic angiotensin II infusions Am J Physiol Renal Physiol, January 1, 2007; 292(1): F330 - F339. [Abstract] [Full Text] [PDF]

				P. Fu, F. Liu, S. Su, W. Wang, X. R. Huang, M. L. Entman, R. J. Schwartz, L. Wei, and H. Y. Lan Signaling Mechanism of Renal Fibrosis in Unilateral Ureteral Obstructive Kidney Disease in ROCK1 Knockout Mice J. Am. Soc. Nephrol., November 1, 2006; 17(11): 3105 - 3114. [Abstract] [Full Text] [PDF]

				W. Qi, X. Chen, J. Holian, E. Mreich, S. Twigg, R. E. Gilbert, and C. A. Pollock Transforming growth factor-beta1 differentially mediates fibronectin and inflammatory cytokine expression in kidney tubular cells Am J Physiol Renal Physiol, November 1, 2006; 291(5): F1070 - F1077. [Abstract] [Full Text] [PDF]

				M. Giannopoulou, S. C. Iszkula, C. Dai, X. Tan, J. Yang, G. K. Michalopoulos, and Y. Liu Distinctive role of Stat3 and Erk-1/2 activation in mediating interferon-{gamma} inhibition of TGF-beta1 action Am J Physiol Renal Physiol, May 1, 2006; 290(5): F1234 - F1240. [Abstract] [Full Text] [PDF]

				W. Wang, X. R. Huang, E. Canlas, K. Oka, L. D. Truong, C. Deng, N. A. Bhowmick, W. Ju, E. P. Bottinger, and H. Y. Lan Essential Role of Smad3 in Angiotensin II-Induced Vascular Fibrosis Circ. Res., April 28, 2006; 98(8): 1032 - 1039. [Abstract] [Full Text] [PDF]

				S. Diskin, J. Kumar, Z. Cao, J. S. Schuman, T. Gilmartin, S. R. Head, and N. Panjwani Detection of differentially expressed glycogenes in trabecular meshwork of eyes with primary open-angle glaucoma. Invest. Ophthalmol. Vis. Sci., April 1, 2006; 47(4): 1491 - 1499. [Abstract] [Full Text] [PDF]

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