B7-1 (CD80) is a transmembrane protein of B cells and other antigen presenting cells, which was originally identified as a regulator of T cell activation and tolerance through CD28 or CTLA-4 binding on T cells. We previously reported that under pathological conditions with FP effacement and proteinuria, kidney podocyte express B7-1. The clinical significance of these results was underscored by the observation that podocyte B7-1 expression correlates with the severity of human lupus nephritis Here we propose to test our central hypothesis that B7-1 in podocytes contributes to the pathogenesis of proteinuria by altering podocyte actin dynamics, podocyte adhesion to the GBM, and slit diaphragm structure and function. To test this hypothesis we propose the following three Specific Aims.
The first Aim will define the molecular mechanism whereby B7-1 orchestrates the reorganization of the podocyte actin cytoskeleton.
Specific Aim two seeks to explore the role of B7-1 in podocyte adhesion to extracellular matrix.
The third Aim will determine the contribution of podocyte B7-1 expression to the pathogenesis and progression of proteinuric kidney diseases. If our hypothesis is correct, the work proposed here will have broad significance in the long-term, because it will establish insight into the dynamics of the interaction between B7-1, the podocyte actin cytoskeleton and the SD complex in proteinuric kidney diseases. This should in the long-term enable us to develop novel, selective podocyte-protective therapies that tackle proteinuria and glomerulosclerosis by blocking the activity of B7-1 in podocytes.

Public Health Relevance

The work proposed here should provide insight into the molecular mechanism whereby B7-1 expression in podocytes causes proteinuria. This should in the long-term enable us to develop novel, selective podocyte-protective therapies that tackle proteinuria and progression of glomerulosclerosis by blocking the activity of B7-1 in podocytes.

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Research Project (R01)
Project #
Application #
Study Section
Pathobiology of Kidney Disease Study Section (PBKD)
Program Officer
Mullins, Christopher V
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Miami School of Medicine
Internal Medicine/Medicine
Schools of Medicine
Coral Gables
United States
Zip Code
Dotimas, James R; Lee, Austin W; Schmider, Angela B et al. (2016) Diabetes regulates fructose absorption through thioredoxin-interacting protein. Elife 5:
Mundel, Peter; Greka, Anna (2015) Developing therapeutic 'arrows' with the precision of William Tell: the time has come for targeted therapies in kidney disease. Curr Opin Nephrol Hypertens 24:388-92
Yoon, Kyoung Wan; Byun, Sanguine; Kwon, Eunjeong et al. (2015) Control of signaling-mediated clearance of apoptotic cells by the tumor suppressor p53. Science 349:1261669
Weins, Astrid; Wong, Jenny S; Basgen, John M et al. (2015) Dendrin ablation prolongs life span by delaying kidney failure. Am J Pathol 185:2143-57
Hakroush, Samy; Cebulla, Angelika; Schaldecker, Thomas et al. (2014) Extensive podocyte loss triggers a rapid parietal epithelial cell response. J Am Soc Nephrol 25:927-38
Brouwers, Olaf; Niessen, Petra M G; Miyata, Toshio et al. (2014) Glyoxalase-1 overexpression reduces endothelial dysfunction and attenuates early renal impairment in a rat model of diabetes. Diabetologia 57:224-35
Greka, Anna; Weins, Astrid; Mundel, Peter (2014) Abatacept in B7-1-positive proteinuric kidney disease. N Engl J Med 370:1263-6
Kampe, Kapil; Sieber, Jonas; Orellana, Jana Marina et al. (2014) Susceptibility of podocytes to palmitic acid is regulated by fatty acid oxidation and inversely depends on acetyl-CoA carboxylases 1 and 2. Am J Physiol Renal Physiol 306:F401-9
Fiorina, Paolo; Vergani, Andrea; Bassi, Roberto et al. (2014) Role of podocyte B7-1 in diabetic nephropathy. J Am Soc Nephrol 25:1415-29
Balbas, Minna D; Burgess, Michael R; Murali, Rajmohan et al. (2014) MAGI-2 scaffold protein is critical for kidney barrier function. Proc Natl Acad Sci U S A 111:14876-81

Showing the most recent 10 out of 37 publications