a molecular signature of proteinuria in glomerulonephritis肾小球肾炎蛋白尿的分子签名.pdfVIP

A Molecular Signature of Proteinuria in Glomerulonephritis 1,2 3,4 1,2 { 5 Heather N. Reich *, David Tritchler , Daniel C. Cattran , Andrew M. Herzenberg , Felix Eichinger , 5 5 5 5 6 Anissa Boucherot , Anna Henger , Celine C. Berthier , Viji Nair , Clemens D. Cohen , James W. Scholey1,2., Matthias Kretzler5. 1 Division of Nephrology, University Health Network, University of Toronto, Toronto, Ontario, Canada, 2 The Toronto Glomerulonephritis Registry, Toronto, Ontario, Canada, 3 Division of Epidemiology and Statistics, Ontario Cancer Institute, and University of Toronto, Toronto, Ontario, Canada, 4 Department of Laboratory Medicine and Pathology, University Health Network, University of Toronto, Toronto, Ontario, Canada, 5 Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, United States of America, 6 Division of Nephrology and Institute of Physiology, University Hospital Zurich, Zurich, Switzerland Abstract Proteinuria is the most important predictor of outcome in glomerulonephritis and experimental data suggest that the tubular cell response to proteinuria is an important determinant of progressive fibrosis in the kidney. However, it is unclear whether proteinuria is a marker of disease severity or has a direct effect on tubular cells in the kidneys of patients with glomerulonephritis. Accordingly we studied an in vitro model of proteinuria, and identified 231 ‘‘albumin-regulated genes’’ differentially expressed by primary human kidney tubular epithelial cells exposed to albumin. We translated these findings to human disease by studyin