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Home » Exploring the Role of Transcription Factors in Lymphatic Diseases
Scientific Advances

Exploring the Role of Transcription Factors in Lymphatic Diseases

By Sarah PlumridgeMay 24, 2016
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Tsutome Kume, PhD, associate professor of Medicine in the Division of Cardiology, observed Foxc1 and Foxc2 expression in the lymphatic system of developing mouse embryos to investigate lymphatic cells and their role in disease.
Tsutome Kume, PhD, associate professor of Medicine in the Division of Cardiology, observed Foxc1 and Foxc2 expression in the lymphatic system of developing mouse embryos to investigate lymphatic cells and their role in disease.

In a recent study published in the Journal of Clinical Investigation, Northwestern Medicine scientists identified a pathway through which transcription factor proteins regulate lymphangiogenesis, the formation of lymphatic vessels from pre-existing lymphatic vessels.

These results suggest a new mechanism for diseases associated with lymphatic vessels, which transport fluid out of tissues as part of the body’s lymphatic system. This system is important for fluid management, immune function and fat absorption, and also plays a role in the spread of tumor cells.

“The area of lymphatic research is expanding, with lymphatics having an important role in tumor growth and vascular disorders,” said senior author Tsutomu Kume, PhD, associate professor of Medicine in the Division of Cardiology and of Pharmacology. “In patients with lymphatic disorders, our results are important for new developments for therapeutic approaches.”

Using mouse models, Kume observed the expression of transcription factors Foxc1 and Foxc2, proteins that bind to specific DNA sequences, in the lymphatic system of developing embryos. Kume removed the Foxc1 and Foxc2 genes, which resulted in increased activation of a chain of proteins, called Extracellular Signal-regulated Kinase pathway (ERK). This in turn led to the proliferation of lymphatic endothelial cells, enlarged lymphatic vessels and abnormally-shaped lymphatic vessels.

The team also discovered how the Foxc1 and Foxc2 genes control signaling pathways of the ERK proteins leading to lymphatic vessel growth.

“This finding expands our knowledge of lymphatic vessel formation and provides new insights into other disease processes,” said Kume, who is a member of the Feinberg Cardiovascular Research Institute, the Center for Genetic Medicine and the Robert H. Lurie Comprehensive Cancer Center of Northwestern University.

In future research, he plans to characterize the deletion of Foxc1 and Foxc2 in the knockout mouse model.

The research was supported by National Institutes of Health grants HL 126920 and EY019484 and American Heart Association grant AHA-14POST20390029.

Cardiology Research
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