Elisha Koshy
Research Mentor: Gary Gerlach
Mentor Department: Nephrology, Medicine
Author(s): Not Available
Session: Session 3 (11:00 AM – 11:50 AM)
Presentation Type: Poster 119
Abstract
Kidney podocytes are specialized cells that help filter blood while keeping important proteins in the body. Podocytes have small extensions called foot processes (FPs) that interlock to form a barrier. When this barrier is damaged, proteins leak into the urine (proteinuria), a sign of kidney disease. Our lab developed a method using a genetically encoded Podocin-BioID to study the proteins in podocyte foot processes within a mouse model. Using this approach, we discovered a protein called Immunoglobulin-like domain containing receptor 2 (ILDR2), that localizes to junctions. We found that ILDR2 levels increase in older mice and in older human kidneys, and build up in diseases that affect podocytes, such as: focal segmental glomerulosclerosis (FSGS) and minimal change disease (MCD). After removing ILDR2 specifically (Ildr2, Ildr2^ Pod/KO) from podocytes in mice, the kidney filtration barrier was damaged: the membrane thickened, scar-like proteins accumulated, and foot processes changed shape. These findings suggest ILDR2 keeps podocytes healthy. To study this, our lab tested both chronic and acute kidney injury models. In chronic injury, podocyte-specific Notch1 overexpression (ICN1^Pod/OE) combined with loss of ILDR2 led to higher protein levels in urine and earlier death. In acute injury caused by toxins, mice without ILDR2 (i.e., Ildr2^PodKO) leaked more protein into urine. Comparing these results with human data could reveal shared molecular patterns in podocytes and their foot processes.
