|
|
Prepublished online as a Blood First Edition Paper on October 31, 2002; DOI 10.1182/blood-2002-02-0629.
Submitted March 6, 2002
Accepted October 18, 2002
Cellular response to hypoxia involves signaling via Smad proteins
Hong Zhang, Hasan O Akman, Eric L P Smith, Jin Zhao, Joanne E Murphy-Ullrich, M A Q Siddiqui, and Olcay A Batuman*
Department of Anatomy and Cell Biology, SUNY Downstate Medical Center, Brooklyn, NY, USA; Division of Hematology/Oncology, Department of Medicine, SUNY Downstate Medical Center, Brooklyn, NY, USA; Center for Cardiovascular and Molecular Medicine, SUNY Downstate Medical Center, Brooklyn, NY, USA
Division of Hematology/Oncology, Department of Medicine, SUNY Downstate Medical Center, Brooklyn, NY, USA; Center for Cardiovascular and Molecular Medicine, SUNY Downstate Medical Center, Brooklyn, NY, USA
Department of Psychiatry, SUNY Downstate Medical Center, Brooklyn, NY, USA
Division of Hematology/Oncology, Department of Medicine, SUNY Downstate Medical Center, Brooklyn, NY, USA
Department of Pathology, University of Alabama at Birmingham, Birmingham, AL, USA
Department of Anatomy and Cell Biology, SUNY Downstate Medical Center, Brooklyn, NY, USA; Center for Cardiovascular and Molecular Medicine, SUNY Downstate Medical Center, Brooklyn, NY, USA
* Corresponding author; email: obatuman{at}aol.com.
The transforming growth factor- (TGF-) family of cytokines regulates vascular development and inflammatory responses. We have recently shown that exposure of human umbilical vein endothelial cells (HUVEC) to hypoxia (1% O2) increases gene expression and bioactivation of TGF-2 and induces its downstream effectors, Smad proteins (Smads), to associate with DNA. In the present study, we show that hypoxia-induced TGF-2 gene expression is dependent on thrombospondin-1-mediated bioactivation of latent TGF-. Blocking TGF-2 but not TGF-1 in hypoxic endothelial cell cultures inhibited induction of the TGF-2 gene, indicating that an autocrine mechanism driven by bioactivation of TGF-2 leads to its gene expression in hypoxic HUVEC. Exposure of HUVEC to hypoxia resulted in phosphorylation and nuclear transportation of Smad2 and Smad3 proteins as well as stimulation of transcriptional activities of Smad3 and the transcription factor hypoxia-inducible factor-1 , and culminated in upregulation of TGF-2 gene expression. Autocrine regulation of TGF-2 production in hypoxia may involve cross-talk between Smad3 and HIF-1 signaling pathways, and could be an important mechanism by which endothelial cells respond to hypoxic stress.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
E. Rimon, B. Chen, A. L. Shanks, D. M. Nelson, and Y. Sadovsky
Hypoxia in Human Trophoblasts Stimulates the Expression and Secretion of Connective Tissue Growth Factor
Endocrinology,
June 1, 2008;
149(6):
2952 - 2958.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. W. J. Young, O. W. Williams, D. Chandra, L. K. Bellinghausen, G. Perez, A. Suarez, M. J. Tuvim, M. G. Roy, S. N. Alexander, S. J. Moghaddam, et al.
Central Role of Muc5ac Expression in Mucous Metaplasia and Its Regulation by Conserved 5' Elements
Am. J. Respir. Cell Mol. Biol.,
September 1, 2007;
37(3):
273 - 290.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. Meier, J. Rossert, P.-F. Plouin, and M. Burnier
Atherosclerotic renovascular disease: beyond the renal artery stenosis
Nephrol. Dial. Transplant.,
April 1, 2007;
22(4):
1002 - 1006.
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. J. Evans, R. C. Russell, O. Roche, T. N. Burry, J. E. Fish, V. W. K. Chow, W. Y. Kim, A. Saravanan, M. A. Maynard, M. L. Gervais, et al.
VHL Promotes E2 Box-Dependent E-Cadherin Transcription by HIF-Mediated Regulation of SIP1 and Snail
Mol. Cell. Biol.,
January 1, 2007;
27(1):
157 - 169.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
V. H. Haase
Hypoxia-inducible factors in the kidney
Am J Physiol Renal Physiol,
August 1, 2006;
291(2):
F271 - F281.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Suzuki, G.-i. Kusakai, Y. Shimojo, J. Chen, T. Ogura, M. Kobayashi, and H. Esumi
Involvement of Transforming Growth Factor-{beta}1 Signaling in Hypoxia-induced Tolerance to Glucose Starvation
J. Biol. Chem.,
September 9, 2005;
280(36):
31557 - 31563.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Zhou, S. Lechpammer, J. S. Greenberger, and J. Glowacki
Hypoxia Inhibition of Adipocytogenesis in Human Bone Marrow Stromal Cells Requires Transforming Growth Factor-{beta}/Smad3 Signaling
J. Biol. Chem.,
June 17, 2005;
280(24):
22688 - 22696.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Zhang, V. Vakil, M. Braunstein, E. L. P. Smith, J. Maroney, L. Chen, K. Dai, J. R. Berenson, M. M. Hussain, U. Klueppelberg, et al.
Circulating endothelial progenitor cells in multiple myeloma: implications and significance
Blood,
April 15, 2005;
105(8):
3286 - 3294.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. Kaur, F. W. Khwaja, E. A. Severson, S. L. Matheny, D. J. Brat, and E. G. Van Meir
Hypoxia and the hypoxia-inducible-factor pathway in glioma growth and angiogenesis
Neuro-oncol,
April 1, 2005;
7(2):
134 - 153.
[Abstract]
[PDF]
|
|
|
|
|
|
|
D. F. Higgins, M. P. Biju, Y. Akai, A. Wutz, R. S. Johnson, and V. H. Haase
Hypoxic induction of Ctgf is directly mediated by Hif-1
Am J Physiol Renal Physiol,
December 1, 2004;
287(6):
F1223 - F1232.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Nakagawa, H. Y. Lan, H. J. Zhu, D.-H. Kang, G. F. Schreiner, and R. J. Johnson
Differential regulation of VEGF by TGF-{beta} and hypoxia in rat proximal tubular cells
Am J Physiol Renal Physiol,
October 1, 2004;
287(4):
F658 - F664.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. Brodsky, A. Leontovich, M. Shtutman, and E. Feinstein
Identification and handling of artifactual gene expression profiles emerging in microarray hybridization experiments
Nucleic Acids Res.,
March 3, 2004;
32(4):
e46 - e46.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
