The long term objective of the present proposal is to advance our understanding of the pathogenetic mechanisms involved in proteinuria of glomerular origin and immune-complex deposition/formation/precipitation. Emphasis will be laid on the molecular biology of various components of the glomerular capillary wall which apparently play a vital role in these mechanisms. The alterations in the capillary wall which occur during nephrotic or nephritic states will be determined. In vivo and in vitro interactions of exogenous and endogenous macromolecules with various components of the glomerular capillary wall will be investigated in order to delineate the mechanisms involved in the induction of proteinuria and immune complex deposition. A wide variety of techniques including electron microscopy, EM-autoradiography, freeze-fracture autoradiography, immunocytochemistry, chromatography, gel electrophoresis, sedimentation ultracentrifugal analysis and protein monolayer spreading rotary shadow techniques will be employed. It is anticipated that the execution of the experiments outlined in this investigation will provide certain answers to questions which are directly related to nephrotic and nephritic conditions in man.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis, Diabetes, Digestive and Kidney Diseases (NIADDK)
Type
Research Project (R01)
Project #
5R01AM028492-05
Application #
3151910
Study Section
Pathology A Study Section (PTHA)
Project Start
1981-04-01
Project End
1989-03-31
Budget Start
1985-04-01
Budget End
1986-03-31
Support Year
5
Fiscal Year
1985
Total Cost
Indirect Cost
Name
Northwestern University at Chicago
Department
Type
School of Medicine & Dentistry
DUNS #
005436803
City
Chicago
State
IL
Country
United States
Zip Code
60611
Lelongt, B; Carone, F A; Kanwar, Y S (1988) Decreased de novo synthesis of proteoglycans in drug-induced renal cystic disease. Proc Natl Acad Sci U S A 85:9047-51
Carone, F A; Ozono, S; Samma, S et al. (1988) Renal functional changes in experimental cystic disease are tubular in origin. Kidney Int 33:8-13
Makino, H; Lelongt, B; Kanwar, Y S (1988) Nephritogenicity of proteoglycans. II. A model of immune complex nephritis. Kidney Int 34:195-208
Makino, H; Lelongt, B; Kanwar, Y S (1988) Nephritogenicity of proteoglycans. III. Mechanism of immune deposit formation. Kidney Int 34:209-19
Carone, F A; Makino, H; Kanwar, Y S (1988) Basement membrane antigens in renal polycystic disease. Am J Pathol 130:466-71
Lelongt, B; Makino, H; Dalecki, T M et al. (1988) Role of proteoglycans in renal development. Dev Biol 128:256-76
Lelongt, B; Makino, H; Kanwar, Y S (1987) Status of glomerular proteoglycans in aminonucleoside nephrosis. Kidney Int 31:1299-310
Kanwar, Y S; Rosenzweig, L J; Jakubowski, M L (1987) Effect of beta-D-xyloside on the renal glomerular cells. II. Morphological studies. Lab Invest 56:160-9
Lelongt, B; Makino, H; Kanwar, Y S (1987) Maturation of the developing renal glomerulus with respect to basement membrane proteoglycans. Kidney Int 32:498-506
Kanwar, Y S; Rosenzweig, L J; Jakubowski, M L (1986) Xylosylated-proteoglycan-induced Golgi alterations. Proc Natl Acad Sci U S A 83:6499-503

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