Grant: Operating Grant

The glomerulus is the filtration unit of the kidney. It filters water and small molecules including body wastes while retaining large molecules essential for body function. When this barrier function is impaired, leakage of proteins into the urine (proteinuria) occurs, which frequently leads to kidney failure. Visceral glomerular epithelial cells (usually called 'podocytes') are critical for structural integrity as well as barrier function of the glomerulus. Recent researches highlighted the importance of a cell surface molecule called 'nephrin'in maintaining barrier function of podocytes. In particular, several groups including ours have demonstrated that phosphorylation of nephrin has a critical role in its function. This proposal aims to define how nephrin phosphorylation is regulated. We will focus on an enzyme called phosphotyrosine phosphatase 1B (PTP1B). We believe that PTP1B is expressed more when podocytes are injured, causing decreased phosphorylation of nephrin. This will lead to impaired function of nephrin and morphological changes of podocytes, eventually leading to proteinuria. We hope that PTP1B could be a therapeutic target in proteinuric kidney disease such as minimal change disease, focal segmental glomerulosclerosis or diabetic nephropathy.