Chinese scholars: Single gene deletion can promote the growth of functional lymphatic valves

Tampa, Florida (August 9, 2021) - A preclinical study by the University of South Florida (USF Health) unexpectedly found that the Foxo1 gene is a potential therapeutic target for hereditary lymphedema

Lymphedema is a chronic disease in which lymph fluid accumulates in the soft tissues under the skin, usually in the arms and legs, causing mild and painful disfigurement and swelling

Although lymphedema can be controlled by massage and tights, there is currently no treatment to solve its root cause: the accumulation of fluid will eventually flow back to the lymphatic system, just like overflowing sinks and clogged drains

"The late fibrotic stage of lymphedema cannot be eliminated by massage," said research leader Dr.

Valve loss or dysfunction blocking the flow of lymph is closely related to the patient's lymphedema

Research led by USF health shows that both scenarios are possible

Based on early USF Health's discovery of the cell signaling process that controls the formation of lymphatic vessels, Dr.

"What's exciting is that Foxo1 is the only gene reported so far.

The lymphatic circulatory system-parallel to the vascular circulatory system-helps maintain a healthy fluid balance in the body by collecting and controlling the flow of extra lymph fluid leaking from the tissues

The main findings include:

• FOXO1 protein (encoded by a gene of Foxol ) to inhibit the development of lymphatic vessels by inhibiting a number of genes that participate in a multi-step process of forming mature lymphatics

  
  

• Inactivation (knockout) Foxo1 lymphatic endothelial cells (LEC) promote multiple stages of valve formation

  
  

• In the lymphedema-bifidus mouse model, the lymphatic valve was reduced by 50%, and the remaining valves were abnormally closed and exhibited fluid reflux

  
  

This research was funded by the National Heart, Lung, and Blood Institute, which is part of the National Institutes of Health

DOI

10.
1172 / JCI142341

Article title

Foxo1 deletion promotes the growth of new lymphatic valves