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Protein complex converts fibroblasts to smooth muscle cells
By Ruth SoRelle, MPH

Robert Schwartz, PhD

A complex of proteins important in determining cellular structure also played a critical role in facilitating the differentiation of non-muscle fibroblasts (cells from which connective tissue is developed) into smooth muscle cells, which make up blood vessels, Baylor College of Medicine researchers reported in a recent issue of the journal Developmental Cell.

"Down the road, this could be important in the therapy of the whole cardiovascular system," said Robert J. Schwartz, PhD, director of the Center for Cardiovascular Development at Baylor and senior author of the report.

The knowledge could be valuable in repairing damaged blood vessels and even aneurysms, weakened portions of blood vessels that can balloon out and even burst. Eventually, the aim is to use this knowledge to aid in repair or replacement of damaged blood vessels in the heart, said Schwartz. He said his lab is now attempting to determine how combinations of early heart-related proteins called transcription factors may convert fibroblasts to cardiac cells.

"This research was supported through a program project grant at Baylor College of Medicine," said Schwartz. "It culminates more than 10 years of research activity."
The proteins that were chosen first appear during the process of the formation (called differentiation) of coronary vessels and also during the appearance of the earliest heart cells, said Schwartz. The transcription factors are serum response factor GATA 6 and cysteine-rich LIM-only proteins called CRP1 AND CRP2. The finding is in concert with current thinking about the way these genes work together in combination and no single factor alone is sufficient to accomplish the goal alone, said Schwartz.

"These proteins are critical for the formation of arteries and veins," he said. Included in those are the vital coronary arteries that provide energy to the cells of the heart.
While the CRPs were previously thought to be largely involved in the maintenance of cell structure and integrity, Schwartz and members of his laboratory found that they also play a role in the nucleus, driving the differentiation process that results in smooth muscle cells.

"We were able to achieve an understanding of how they work together and interact to activate downstream smooth muscle gene targets," he said. These genes further the process of differentiation into smooth muscle cells.

As further proof of the effect of the factors, researchers found high levels of proteins important to the differentiation process being made. The cell changed its shape to simulate that of smooth muscle cells, said Schwartz.

Schwartz said a graduate student in his laboratory, David F. Chang, worked out the interaction of the three factors to direct smooth muscle formation. He worked with Narasinhaswamy S. Belaguli, PhD, an assistant professor in the department of surgery, in beginning this activity.

Mark Majesky, PhD, an associate professor in the department of pathology, developed an experimental system to follow the differentiation of the coronary vessels that enabled a major portion of the work involved in this study, Schwartz said.

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