Understanding the molecular communication between epithelium and lymphatics in kidney disease

Cells in the kidney are constantly ‘talking’ to one another, facilitated by the exchanges of molecular messages between neighbouring cells. The process by which cells talk to one another can break down in kidney disease and understanding and restoring this communication may be important for new therapies. However, there are many communications that occur between kidney cells that scientists have not yet identified.

We have identified a new avenue of communication in the kidney. The talking happens between podocytes; the cells responsible for filtering blood, and lymphatics; the kidney’s waste disposal system which is important for keeping inflammation in check. We also have identified one of the messengers that might be responsible for this talking, called CXCL12; a molecule that scientists have already identified as a potential target in kidney disease. We think that in kidney disease, podocytes talk to lymphatics by using CXCL12 as a messenger.

To explore how podocytes and lymphatics talk to one another in renal disease, we will study animal models of glomerular disease. We will first explore how close podocytes and lymphatics reside to one another and how this changes in glomerular disease. We will then use genetic sequencing to identify the messages delivered by damaged podocytes and assess what influence these messengers have on lymphatic cells grown in a dish. We will then repeat these experiments, but this time, remove the CXCL12 message from podocytes; impairing their ability to talk to lymphatics. We will examine whether impairing the communication between podocytes and lymphatics makes glomerulonephritis better or worse.

Our experiments will be the first to describe how podocytes and lymphatics talk to one another; an unexplored topic to date. We think that the communication between these two kinds of cells might be important for how kidney diseases progress, and that targeting the messengers, including CXCL12, that facilitate this talking could give rise to new therapies for patients.

References:
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5.  …Jafree, D. J. et al. Beyond a passive conduit: Implications of lymphatic biology for kidney disease. J Am Soc Nephrol 31: 1178-1190 (2020).