Podocalyxin Is Required for Maintaining Blood–Brain Barrier Function During Acute Inflammation
This week we profile a recent publication in PNAS from the laboratory of
Dr. Kelly McNagny (pictured) at UBC’s Biomedical Research Centre.
Can you provide a brief overview of your lab’s current research focus?
Our current research focus is concerned with understanding the mechanisms of inflammation. We study the development and trafficking of immune cells and the function of tissue barriers. Historically we have focused our work on the CD34 family sialomucins (CD34, podocalyxin and endoglycan) but we are happy to follow wherever the data leads. This path has revealed exciting discoveries in the development of innate lymphoid cells, the influence of the gut microbiome in allergic inflammation, the pathophysiology of kidney disease and mechanisms of tumour metastasis. In this current study published in PNAS, we determined how blood vessels protect the brain during inflammation.
What is the significance of the findings in this publication?
The blood-brain barrier (BBB) separates the brain from circulating blood and it is essential for maintaining healthy brain function. Expression of podocalyxin on the inner “tube” of blood vessels (vascular endothelia) has been known for a long time. It is particularly highly-expressed in the blood vessels in the brain. When we delete this protein from blood vessels in mice they develop normally and appeared to be perfectly healthy. However, we found that podocalyxin has an important role in maintaining BBB integrity during inflammation.
What are the next steps for this research?
Leakage of plasma components like activated proteases can promote the damage of brain tissue in infections and neurological diseases including stroke, epilepsy and multiple sclerosis. Although we now know that podocalyxin has a role in maintaining tight barriers during brain inflammation, we do not yet fully understand how it works. If we can determine these mechanisms, we will be able to develop new therapies to control barrier function. In addition to improving barrier function in inflammatory disease, we may be able to open barriers to allow certain life-saving drugs to enter brain tissue.
This work was funded by:
This work was funded in part by a research grant from the Canadian Institutes for Health Research (CIHR). We received additional support from the Centre of Blood Research at UBC.