Nat Commun: How are blood vessels and lymph nodes separated during development?

7, 2021 /--- -- Based on a recent study, researchers at Kumamoto University in Japan have clarified the mechanism by which blood and lymphatic tubes separate from each other after development.
the characteristics and structures of the two organ types are very similar, and how they remain separated has not been clarified.
study, researchers found that the molecule Folliculin (FLCN) in endoskin cells in blood vessels acted as a key molecule to maintain this separation.
separate networks of blood and lymphatic tubes until they eventually converg in the corners of the left and right neck veins.
like a pipe that transports oxygen from the lungs to tissues throughout the body.
, on the other hand, the lymphatic tube absorbs tissue fluid that cannot be collected by blood vessels and is part of the immune system.
, however, the characteristics and structure of the blood and lymphatic tubes are very similar, so how to keep them separated remains a mystery.
of this mechanism could provide the basis for the development of new treatments for human lymphatic disease.
(Photo Source: Www.pixabay.com) In this study, researchers focused first on FLCN, a genetic disease-causing gene with typical symptoms of a variety of pulmonary cysts, kidney cancer, and benign skin tumors (Birt-Hogg-Dube syndrome).
they found an abnormal match between blood and lymphatic tubes in mice lacking the Flcn gene in vascular endotent cells, leading to fetal death.
addition, even in mice with normal blood and lymphatic tube separation, the absence of the Flcn gene induced in endothoste cells can lead to an abnormal match between the two blood vessels.
Vlcn deficiency causes lymphatic bias in vascular endotrectric cells.
these cells cause a match between the blood and the lymphatic tubes.
Prox1, a central transcription factor that regulates lymphatic tube production, is inhibited by Flcn in Fl endothor cells to maintain the identity of vascular endothorte cells.
, however, prox1 is expressed when the Flcn regulation function of the endotytial cells of the blood vessels is lost, resulting in lymphatic bias in the endotrheatic cells.
researchers also found that the absence of Flcn causes the transcription factor Tfe3, which is usually found in the cytokine, to be trans-positioned into the nucleo nucleation, thereby directly increasing the expression of Prox1.
In fact, when the Flcn gene knocked out mice and the Tfe3 gene knocked out mice to interbreed, Prox1 did not express without Tfe3 and Flcn, and did not see the venous endothos cells skewed by the lymphatic tubes.
these results suggest that FLCN acts as a key molecule for regulating plasticity and maintaining blood and lymphatic tube separation.
" results are significant academic because they illustrate a biological question that has not been solved for years: Why do two very similar circulatory systems (blood vessels and lymphatic tubes) form and maintain separate networks in the human body? From a clinical point of view? Therefore, it has the potential to provide clues to the process of cancer metastasis and may develop into a treatment for lymphedema.
, an associate professor who led the study, said.
surgery, lymph node removal can lead to severe edema in the upper and lower limbs due to reduced lymph node excretability.
In this study, we envisioned a future innovative therapy for lymphedema that could artificially create a locally connected venous and lymphatic sifier by interfering with FLCN's signaling pathways on drugs.
" (Bioon.com) Source: How blood and lymph vessels remain after development Original source: Ikue Tai-Nagara et al, Blood and lymphatic systems are sorryed by the FLCN tumor suppressor, Nature Communications (2020). DOI: 10.1038/s41467-020-20156-6