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October 15, 2012 (Toronto, ON) – In a study published in the October issue of the prestigious journal Cell, researchers Drs. Susan Quaggin and Tony Pawson at Mount Sinai Hospital’s Samuel Lunenfeld Research Institute, with their teams of post-doctoral researchers, have made an important discovery relating to the effects of a vital signalling protein in the kidney, potentially impacting drug therapies and treatment for the more than 30,000 Canadians who suffer from kidney failure.

The research team uncovered new information about a key binding protein of VEGF (vascular endothelial growth factor) - a protein produced by cells that triggers growth and other changes. Drs. Quaggin and Pawson discovered that FLT1, a protein that acts as one of the targets of VEGF, plays a significant role in the health and development of microscopic kidney filters called glomeruli and is particularly important in kidney podocytes which are specialized cells in the filters, needed for proper urine production. When FLT1 is lacking in these podocytes, the shape of these specialized cells changes dramatically, resulting in proteinuria – a massive amount of critical blood proteins spilling into the urine which ultimately leads to kidney failure. In patients, these diseases are termed ‘nephrotic syndromes’ and are particularly common in children.

“These results will change the way we think about some common forms of kidney disease,” says Dr. Quaggin, who is also the Gabor-Zellerman Chair in Renal Biology, and was awarded the 2009 Kidney Foundation of Canada Medal for Research Excellence. “Many of the molecules that are important in the kidney filter are found hidden inside cells, making them difficult targets for drug design. This study provides a new target that works from outside the cell – offering an opportunity to design drug therapies for patients with nephrotic syndrome and other kidney diseases.”

Researchers used a combination of leading edge scientific methods to show that a soluble version of the FLT1 receptor protein binds to lipid islands on the cell surface of podocytes, which results in a series of signalling events in the VEGF pathway that control the shape of these cells. This receptor also regulates function in vessels outside of the kidney. For example, in addition to a role in kidney cell organization, the study found that soluble FLT1 is important in blood vessels of the eye and liver.

 “This study will not only impact the development of a new pathway important for kidney function, but also highlights the development of new techniques that are now available to us, so that we can further study protein-lipid interactions in living cells,” explains Dr. Quaggin. “Twenty years ago, we couldn’t analyze cells with such precision. We just didn’t have the level of technology available to us now, so that we can modify or improve treatment for patients with kidney disease.”

Also a physician, Dr. Quaggin knows the devastation of disease first-hand – seeing patients succumb to end-stage kidney disease which has a five-year survival rate of only 55 per cent. This study provides important new understanding for the basis and treatment of conditions for kidney diseases and beyond and provides a foundation for future investigation into causes of vascular diseases. In 1997, Dr. Quaggin discovered a gene critical for the development of the kidneys, heart and lungs.

 

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