| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 Department of Pediatrics, Division Pediatric Cardiology, University of Virginia Health System, Charlottesville, VA, USA; Department of Internal Medicine, Cardiology Division, University of Virginia Health System, Charlottesville, VA, USA
2 Department of Pediatrics, Division Pediatric Cardiology, University of Virginia Health System, Charlottesville, VA, USA
3 Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan
4 Department of Internal Medicine, Cardiology Division, University of Virginia Health System, Charlottesville, VA, USA
* To whom correspondence should be addressed. E-mail: aeveret3{at}jhmi.edu.
Hepatoma derived growth factor (HDGF) was previously identified as a developmentally regulated cardiovascular and renal gene that is mitogenic for vascular smooth muscle and aortic endothelial cells. As reciprocal interactions of smooth muscle and endothelial cells are necessary for vascular formation, we examined whether HDGF plays a role in angiogenesis. Using immunohistochemistry, HDGF was highly expressed in endothelial cells of non-muscularized, forming blood vessels of the fetal lung. HDGF was also expressed in endothelial cells of small (20 µm) mature arteries and veins. By Western immuno-blotting, HDGF was highly expressed by human pulmonary microvascular endothelial cells in vitro. Adenoviral overexpression of HDGF was mitogenic for human pulmonary microvascular endothelial cells in serum free media, stimulating a 1.75 fold increase in BrdU uptake and a two fold increase in cell migration. Using the chick chorioallantoic membrane (CAM) a biologic assay for angiogenesis, exogenous recombinant HDGF significantly stimulated blood vessel formation and a dose dependent reorganization of cells within the CAM into a more compact, linear alignment reminiscent of tube formation. Using double immunostaining for endothelial cells with a TGFBIIR antibody and BrdU as a marker of cell proliferation, exogenous HDGF selectively stimulated endothelial cell BrdU uptake. HDGF also activated specific Erk1/2 signaling and did not overlap with VEGF SAPK/JNK, Akt mediated pathways. We conclude that HDGF is a highly expressed vascular endothelial cell protein in vivo and is a potent endothelial mitogen and regulator of endothelial cell migration by mechanisms distinct from VEGF.
This article has been cited by other articles:
|
|
 |
|
  S. Yamamoto, Y. Tomita, Y. Hoshida, E. Morii, T. Yasuda, Y. Doki, K. Aozasa, H. Uyama, H. Nakamura, and M. Monden Expression Level of Hepatoma-Derived Growth Factor Correlates with Tumor Recurrence of Esophageal Carcinoma Ann. Surg. Oncol., July 1, 2007; 14(7): 2141 - 2149. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Uyama, Y. Tomita, H. Nakamura, S. Nakamori, B. Zhang, Y. Hoshida, H. Enomoto, Y. Okuda, M. Sakon, K. Aozasa, et al. Hepatoma-Derived Growth Factor Is a Novel Prognostic Factor for Patients with Pancreatic Cancer. Clin. Cancer Res., October 15, 2006; 12(20): 6043 - 6048. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. M. Lukasik, T. Cierpicki, M. Borloz, J. Grembecka, A. Everett, and J. H. Bushweller High resolution structure of the HDGF PWWP domain: A potential DNA binding domain Protein Sci., February 1, 2006; 15(2): 314 - 323. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Zhang, H. Ren, P. Yuan, W. Lang, L. Zhang, and L. Mao Down-regulation of Hepatoma-Derived Growth Factor Inhibits Anchorage-Independent Growth and Invasion of Non-Small Cell Lung Cancer Cells Cancer Res., January 1, 2006; 66(1): 18 - 23. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. M. Abouzied, H. M. El-tahir, L. Prenner, H. Haberlein, V. Gieselmann, and S. Franken Hepatoma-derived Growth Factor: SIGNIFICANCE OF AMINO ACID RESIDUES 81-100 IN CELL SURFACE INTERACTION AND PROLIFERATIVE ACTIVITY J. Biol. Chem., March 25, 2005; 280(12): 10945 - 10954. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| Visit Other APS Journals Online |
