HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) A correction has been published Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Sakurai, D. Articles by Tokunaga, K. Search for Related Content PubMed PubMed Citation Articles by Sakurai, D. Articles by Tokunaga, K. Pubmed/NCBI databases Gene GEO Profiles HomoloGene UniGene Substance via MeSH

Crucial Role of Inhibitor of DNA Binding/Differentiation in the Vascular Endothelial Growth Factor-Induced Activation and Angiogenic Processes of Human Endothelial Cells¹

Daisuke Sakurai^*,¶, Naoyuki Tsuchiya^2,*, Akihiro Yamaguchi, Yurai Okaji, Nelson H. Tsuno, Tetsuji Kobata^¶, Koki Takahashi and Katsushi Tokunaga^*

Departments of ^* Human Genetics, Allergy and Rheumatology, Surgical Oncology, and Transfusion Medicine, Graduate School of Medicine, University of Tokyo, Tokyo, Japan; and ^¶ Division of Immunology, Institute for Medical Science, Dokkyo University School of Medicine, Tochigi, Japan

Angiogenesis plays a pivotal role in the aggressive proliferation of synovial cells in rheumatoid arthritis. We have previously reported the overexpression of inhibitor of DNA binding/differentiation (Id) in the endothelial cells within the synovial tissues of rheumatoid arthritis. In this study, we investigated the role of Id in inflammation and angiogenesis in an in vitro model using HUVECs. Vascular endothelial growth factor (VEGF) and TGF induced the expression of Id1 and Id3 in HUVECs. Forced expression of Id induced proliferative activity in HUVECs accompanied by down-regulation of p16^INK4a. Overexpression of Id enhanced expression of ICAM-1 and E-selectin, and induced angiogenic processes such as transmigration, matrix metalloproteinase-2 and -9 expression, and tube formation. In contrast, knockdown of Id1 and Id3 with RNA interference abolished proliferation, activation, and angiogenic processes of HUVECs induced by VEGF. These results indicated that Id plays a crucial role in VEGF-induced signals of endothelial cells by causing activation and potentiation of angiogenic processes. Based on these findings, it was proposed that inhibition of expression and/or function of Id1 and Id3 may potentially be of therapeutic value for conditions associated with pathological angiogenesis.

This article has been cited by other articles:

				R. C. Doebele, F. T. Schulze-Hoepfner, J. Hong, A. Chlenski, B. D. Zeitlin, K. Goel, S. Gomes, Y. Liu, M. K. Abe, J. E. Nor, et al. A novel interplay between Epac/Rap1 and mitogen-activated protein kinase kinase 5/extracellular signal-regulated kinase 5 (MEK5/ERK5) regulates thrombospondin to control angiogenesis Blood, November 12, 2009; 114(20): 4592 - 4600. [Abstract] [Full Text] [PDF]

				D. Del Duca, G. Wong, P. Trieu, D. Rodaros, A. Kouremenos, A. Tadevosyan, G. Vaniotis, L. R. Villeneuve, C. I. Tchervenkov, S. Nattel, et al. Association of neonatal hypoxia with lasting changes in left ventricular gene expression: An animal model J. Thorac. Cardiovasc. Surg., September 1, 2009; 138(3): 538 - 546. [Abstract] [Full Text] [PDF]

				R. Miller, V. Cirulli, G. R. Diaferia, S. Ninniri, G. Hardiman, B. E. Torbett, R. Benezra, and L. Crisa Switching-On Survival and Repair Response Programs in Islet Transplants by Bone Marrow-Derived Vasculogenic Cells Diabetes, September 1, 2008; 57(9): 2402 - 2412. [Abstract] [Full Text] [PDF]

				I. Airoldi, C. Cocco, N. Giuliani, M. Ferrarini, S. Colla, E. Ognio, G. Taverniti, E. Di Carlo, G. Cutrona, V. Perfetti, et al. Constitutive expression of IL-12R{beta}2 on human multiple myeloma cells delineates a novel therapeutic target Blood, August 1, 2008; 112(3): 750 - 759. [Abstract] [Full Text] [PDF]

				L. Kamalian, J. R. Gosney, S. S. Forootan, C. S. Foster, Z. Z. Bao, C. Beesley, and Y. Ke Increased Expression of Id Family Proteins in Small Cell Lung Cancer and its Prognostic Significance Clin. Cancer Res., April 15, 2008; 14(8): 2318 - 2325. [Abstract] [Full Text] [PDF]

				K. Nishiyama, K. Takaji, Y. Uchijima, Y. Kurihara, T. Asano, M. Yoshimura, H. Ogawa, and H. Kurihara Protein Kinase A-regulated Nucleocytoplasmic Shuttling of Id1 during Angiogenesis J. Biol. Chem., June 8, 2007; 282(23): 17200 - 17209. [Abstract] [Full Text] [PDF]

				F. Zwerts, F. Lupu, A. De Vriese, S. Pollefeyt, L. Moons, R. A. Altura, Y. Jiang, P. H. Maxwell, P. Hill, H. Oh, et al. Lack of endothelial cell survivin causes embryonic defects in angiogenesis, cardiogenesis, and neural tube closure Blood, June 1, 2007; 109(11): 4742 - 4752. [Abstract] [Full Text] [PDF]

				H.-J. Kim, H. Chung, Y.-G. Yoo, H. Kim, J.-Y. Lee, M.-O. Lee, and G. Kong Inhibitor of DNA Binding 1 Activates Vascular Endothelial Growth Factor through Enhancing the Stability and Activity of Hypoxia-Inducible Factor-1{alpha} Mol. Cancer Res., April 1, 2007; 5(4): 321 - 329. [Abstract] [Full Text] [PDF]

				D. S. Kim, J. A. Franklyn, K. Boelaert, M. C. Eggo, J. C. Watkinson, and C. J. McCabe Pituitary Tumor Transforming Gene (PTTG) Stimulates Thyroid Cell Proliferation via a Vascular Endothelial Growth Factor/Kinase Insert Domain Receptor/Inhibitor of DNA Binding-3 Autocrine Pathway J. Clin. Endocrinol. Metab., November 1, 2006; 91(11): 4603 - 4611. [Abstract] [Full Text] [PDF]

				K. Nishiyama, K. Takaji, K. Kataoka, Y. Kurihara, M. Yoshimura, A. Kato, H. Ogawa, and H. Kurihara Id1 Gene Transfer Confers Angiogenic Property on Fully Differentiated Endothelial Cells and Contributes to Therapeutic Angiogenesis Circulation, November 1, 2005; 112(18): 2840 - 2850. [Abstract] [Full Text] [PDF]