| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
on TGF-
Signaling Through Down-Regulation of TGF- Receptor Type II in Human Dermal Fibroblasts1
Department of Dermatology, Faculty of Medicine, University of Tokyo, Tokyo, Japan
Transforming growth factor-
stimulates the production of the extracellular matrix, whereas TNF-
has antifibrotic activity. Understanding the molecular mechanism underlying the antagonistic activities of TNF- against TGF- is critical in the context of tissue repair and maintenance of tissue homeostasis. In the present study, we demonstrated a novel mechanism by which TNF- blocks TGF--induced gene and signaling pathways in human dermal fibroblasts. We showed that TNF- prevents TGF--induced gene trans activation, such as 2(I) collagen or tissue inhibitor of metalloproteinases 1, and TGF- signaling pathways, such as Smad3, c-Jun N-terminal kinase, and p38 mitogen-activated protein kinases, without inducing levels of inhibitory Smad7 in human dermal fibroblasts. TNF- down-regulates the expression of type II TGF- receptor (TRII) proteins, but not type I TGF- receptor (TRI), in human dermal fibroblasts. However, neither TRII mRNA nor TRII promoter activity was decreased by TNF-. TNF--mediated decrease of TRII protein expression was not inhibited by the treatment of fibroblasts with either a selective inhibitor of I-
B- phosphorylation, BAY 11-7082, or a mitogen-activated protein kinase/extracellular signal-regulated kinase inhibitor, PD98059. Calpain inhibitor I (ALLN), a protease inhibitor, inhibits TNF--mediated down-regulation of TRII. We found that TNF- triggered down-regulation of TRII, leading to desensitization of human dermal fibroblasts toward TGF-. Furthermore, these events seemed to cause a dramatic down-regulation of 2(I) collagen and tissue inhibitor of metalloproteinases 1 in systemic sclerosis fibroblasts. These results indicated that TNF- impaired the response of the cells to TGF- by regulating the turnover of TRII.
This article has been cited by other articles:
|
|
 |
|
  T. Hirose, K. Nakazato, H. Song, and N. Ishii TGF- 1 and TNF-{alpha} are involved in the transcription of type I collagen {alpha}2 gene in soleus muscle atrophied by mechanical unloading J Appl Physiol, January 1, 2008; 104(1): 170 - 177. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Fujita, S. Saika, W. W.-Y. Kao, K. Fujita, T. Miyamoto, K. Ikeda, Y. Nakajima, and Y. Ohnishi Endogenous TNF{alpha} Suppression of Neovascularization in Corneal Stroma in Mice Invest. Ophthalmol. Vis. Sci., July 1, 2007; 48(7): 3051 - 3055. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. A. Cooker, D. Peterson, J. Rambow, M. L. Riser, R. E. Riser, F. Najmabadi, D. Brigstock, and B. L. Riser TNF-{alpha}, but not IFN-{gamma}, regulates CCN2 (CTGF), collagen type I, and proliferation in mesangial cells: possible roles in the progression of renal fibrosis Am J Physiol Renal Physiol, July 1, 2007; 293(1): F157 - F165. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Zandvoort, D. S. Postma, M. R. Jonker, J. A. Noordhoek, J. T. W. M. Vos, Y. M. van der Geld, and W. Timens Altered expression of the Smad signalling pathway: implications for COPD pathogenesis Eur. Respir. J., September 1, 2006; 28(3): 533 - 541. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Saika, K. Ikeda, O. Yamanaka, K. C. Flanders, Y. Okada, T. Miyamoto, A. Kitano, A. Ooshima, Y. Nakajima, Y. Ohnishi, et al. Loss of Tumor Necrosis Factor {alpha} Potentiates Transforming Growth Factor {beta}-mediated Pathogenic Tissue Response during Wound Healing Am. J. Pathol., June 1, 2006; 168(6): 1848 - 1860. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y Allanore, G Devos-Francois, C Caramella, P Boumier, V Jounieaux, and A Kahan Fatal exacerbation of fibrosing alveolitis associated with systemic sclerosis in a patient treated with adalimumab. Ann Rheum Dis, June 1, 2006; 65(6): 834 - 835. [Full Text] [PDF]
|
|
|
|
 |
|
 M. Jinnin, H. Ihn, and K. Tamaki Characterization of SIS3, a Novel Specific Inhibitor of Smad3, and Its Effect on Transforming Growth Factor-beta1-Induced Extracellular Matrix Expression Mol. Pharmacol., February 1, 2006; 69(2): 597 - 607. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T Bohgaki, Y Amasaki, N Nishimura, M Bohgaki, Y Yamashita, M Nishio, K-i Sawada, S Jodo, T Atsumi, and T Koike Up regulated expression of tumour necrosis factor {alpha} converting enzyme in peripheral monocytes of patients with early systemic sclerosis Ann Rheum Dis, August 1, 2005; 64(8): 1165 - 1173. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K Breitkopf, I Sawitza, J H Westhoff, L Wickert, S Dooley, and A M Gressner Thrombospondin 1 acts as a strong promoter of transforming growth factor {beta} effects via two distinct mechanisms in hepatic stellate cells Gut, May 1, 2005; 54(5): 673 - 681. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Jinnin, H. Ihn, K. Yamane, Y. Mimura, Y. Asano, and K. Tamaki {alpha}2(I) collagen gene regulation by protein kinase C signaling in human dermal fibroblasts Nucleic Acids Res., March 1, 2005; 33(4): 1337 - 1351. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
