Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

UNC studies identify key genes involved in blood vessel development

08.08.2003


New research from the University of North Carolina at Chapel Hill has identified two genes that play key roles in regulating blood vessel development.



The research appears in two reports published in the Aug. 15 issue of Molecular and Cellular Biology, a professional journal. Dr. Cam Patterson, professor of medicine and director of the Carolina Cardiovascular Biology Center and a member of the UNC Lineberger Comprehensive Cancer Center, led both studies.

Both research papers focus on angiogenesis, the molecular program by which endothelial cells lining blood vessels develop or differentiate from their precursor stem cells.


"I think of endothelial cells as the ’intelligent cells’ of blood vessels," Patterson said. "They are communicators between the blood vessel wall and bloodstream. They are the cells that determine what a blood vessel does. For example, during angiogenesis, when new blood vessels are being formed, it’s the endothelial cells that determine where they go and how big they get."

And as communicators, Patterson added, endothelial cells also help determine what passes through the blood-brain barrier, through the endothelium and into the brain, and what does not.

"One study in this issue of the journal sheds important new light on the molecular process that prevents a particular cell type from overrunning the developing embryo," Patterson said. "The findings from this study also offer tantalizing possibilities for new treatments aimed at putting the brakes on blood vessel development in tumors and other disorders having important vascular growth components, such as diabetes."

The second paper focuses on what activates the endothelial cell program, and it reports having found a possible answer in a single protein, a known transcription factor that has never been characterized functionally.

"This has really been a ’holy grail’ finding for us," Patterson said. "No other research group has found a single transcription factor that by itself is both necessary and sufficient to activate the endothelial cell program." For the first study, co-authors were Patterson and School of Medicine research colleagues Drs. Martin Moser, Olav Binder, Yaxu Wu, Julius Aitsebaomo, Rongqin Ren, Victoria Bautch and Frank L. Conlon. Dr. Christoph Bode of Freiburg University in Germany also served as co-author. The study team discovered a gene they called BMPER for BMP-binding endothelial precursor-derived regulator. The molecule was found using "a sophisticated molecular approach to separate out endothelial cell precursors from non-endothelial cell cells in a stem-cell model," Patterson said.

In a series of experiments, the researchers demonstrated that only endothelial cells and their precursors express the BMPER gene. Endothelial cells secrete the protein as they differentiate, issuing a molecular "stop" order to inhibit further differentiation.

"This was shown very clearly when we used stem cells to generate endothelial cells and then added BMPER. We found that BMPER inhibited the whole process," Patterson said.

In the second study, co-authors Wu, Moser, Bautch and Patterson looked at the gene flk1, a molecular marker for early endothelial cell precursors. "Flk1 is important because it’s a receptor for vascular endothelial growth factor, which is an angiogenic factor," Patterson said.

"But it’s also important to us because it’s the first gene that gets turned on in endothelial progenitor cells. So we wanted to know what transcription factors turn on flk1 and are those factors themselves sufficient enough to turn on the whole endothelial cell gene program - that is, can you use those factors to take a precursor cell and turn it into an endothelial cell?"

The study team used a screening procedure (yeast-1 hybrid screen) in which a piece of DNA was employed as a kind of bait to screen a library containing a variety of transcription factors.

"And the protein we pulled out with the bait is called HOXB5, a transcription factor that’s known but that has never been functionally characterized," Patterson said.

The researchers then asked whether HOXB5 would increase expression of flk1 by binding to genetic regulatory elements in the gene. "And indeed that was the case in our in vitro studies," Patterson said. "But the really important findings came when we over-expressed HOXB5 in stem cells. We used a stem cell model developed a few years ago here at UNC and found we could double or triple the number of flk1-positive cells that were produced from stem cells.

"But most importantly, if we look at actual vessel formation in stem cell cultures, we found vessel formation is hugely increased." Thus, the findings indicate that simply over-expressing HOXB5 by itself not only increases expression of the regulatory protein, but also increases the number of endothelial cells that will form from the precursors.

"We’re especially excited about the possibility that we can use this transcription factor to create renewable populations of endothelial cell precursors. I think this will be very important, as it would be analogous to hematopoietic (blood cell-forming) stem cells," Patterson said.

"And if we can create an analogous endothelial stem cell line, we can use that for gene therapy applications, for example, as a regenerative therapy for aged blood vessels.

"The therapeutic potentials for this research are many."

A grant from the National Heart, Lung and Blood Institute, a component of the National Institutes of Health, supported this research.

Contact: Les Lang, phone: +1-919-843-9687, email: llang@med.unc.edu

Leslie Lang | EurekAlert!
Further information:
http://www.med.unc.edu

More articles from Life Sciences:

nachricht From a plant sugar to toxic hydrogen sulfide
19.12.2018 | Universität Konstanz

nachricht Gut microbiome regulates the intestinal immune system, researchers find
19.12.2018 | Brown University

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: New megalibrary approach proves useful for the rapid discovery of new materials

Northwestern discovery tool is thousands of times faster than conventional screening methods

Different eras of civilization are defined by the discovery of new materials, as new materials drive new capabilities. And yet, identifying the best material...

Im Focus: Data storage using individual molecules

Researchers from the University of Basel have reported a new method that allows the physical state of just a few atoms or molecules within a network to be controlled. It is based on the spontaneous self-organization of molecules into extensive networks with pores about one nanometer in size. In the journal ‘small’, the physicists reported on their investigations, which could be of particular importance for the development of new storage devices.

Around the world, researchers are attempting to shrink data storage devices to achieve as large a storage capacity in as small a space as possible. In almost...

Im Focus: Data use draining your battery? Tiny device to speed up memory while also saving power

The more objects we make "smart," from watches to entire buildings, the greater the need for these devices to store and retrieve massive amounts of data quickly without consuming too much power.

Millions of new memory cells could be part of a computer chip and provide that speed and energy savings, thanks to the discovery of a previously unobserved...

Im Focus: An energy-efficient way to stay warm: Sew high-tech heating patches to your clothes

Personal patches could reduce energy waste in buildings, Rutgers-led study says

What if, instead of turning up the thermostat, you could warm up with high-tech, flexible patches sewn into your clothes - while significantly reducing your...

Im Focus: Lethal combination: Drug cocktail turns off the juice to cancer cells

A widely used diabetes medication combined with an antihypertensive drug specifically inhibits tumor growth – this was discovered by researchers from the University of Basel’s Biozentrum two years ago. In a follow-up study, recently published in “Cell Reports”, the scientists report that this drug cocktail induces cancer cell death by switching off their energy supply.

The widely used anti-diabetes drug metformin not only reduces blood sugar but also has an anti-cancer effect. However, the metformin dose commonly used in the...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

ICTM Conference 2019: Digitization emerges as an engineering trend for turbomachinery construction

12.12.2018 | Event News

New Plastics Economy Investor Forum - Meeting Point for Innovations

10.12.2018 | Event News

EGU 2019 meeting: Media registration now open

06.12.2018 | Event News

 
Latest News

Scientists to give artificial intelligence human hearing

19.12.2018 | Information Technology

Newly discovered adolescent star seen undergoing 'growth spurt'

19.12.2018 | Physics and Astronomy

From a plant sugar to toxic hydrogen sulfide

19.12.2018 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>