Scientists studying the mechanisms behind cell adhesion have made some significant discoveries about the factors that influence podocyte survival. The kidney filter barrier is made up of podocyte cells with long foot-like projections that wrap around the capillaries of the glomerulus. The slits between these projections allow smaller molecules like salts, water and sugar to pass, while preventing larger molecules such as proteins from leaving the blood stream. Podocytes undergo significant physical stress as blood is pushed through the filter barrier. A receptor called integrin a3ß1 ensures that podocyte cells remain tightly bound to the glomerular basement membrane.
Researchers from the Netherlands Cancer Institute in Amsterdam explored the link between a3ß1 and a protein called CD151, which is strongly expressed in podocytes. They showed that CD151 and a3ß1 interact and that CD151 is involved in adhesion strengthening. They studied mice lacking CD151 in podocytes and discovered that the mice developed glomerulosclerosis. They also suffered from kidney abnormalities, including unusually broad foot processes and irregular thickening of the glomerular basement membrane. They found that mice lacking global CD151 were not necessarily susceptible to renal disease unless they had a genetic predisposition. They reasoned that because the mice lacked CD151, their podocytes would be more loosely bound and unable to withstand increased mechanical stress. They proved the theory by increasing blood pressure and filtration pressure, which induced nephropathy in the mice. Treating the mice with an ACE inhibitor drug reduced blood pressure as well as pressure within the glomerulus and prolonged their life span. The scientists determined that the reduction in glomerular pressure was key to preserving podocytes and slowing down glomerulosclerosis in the mice.
Blood Pressure Influences End Stage Renal Disease of CD151 Knockout Mice, Journal of Clinical Investigation, January 3, 2012