Decreased glomerular expression of agrin in diabetic nephropathy and podocytes, cultured in high glucose medium

Autor: M. Hafner, F. J. Van Der Woude, Jhm Berden, L.P.W.J. van den Heuvel, R. Engelleiter, Ruediger Waldherr, S. Resch, S. Kahlert, J. van der Born, Alexander J. Groffen, Benito A. Yard, Stephan Kröger
Přispěvatelé: Functional Genomics, Constitutional and Administrative Law, Human genetics, Amsterdam Neuroscience - Cellular & Molecular Mechanisms
Rok vydání: 2001
Předmět:
Male
Physiology
Biopsy
Kidney Glomerulus
Pathofysiologie
immunologie en behandeling van nieraandoeningen
Diabetic nephropathy
Basement Membrane
Epithelium
chemistry.chemical_compound
Diabetic Nephropathies
Fluorescent Antibody Technique
Indirect
Cells
Cultured
Agrin
Membrane Glycoproteins
biology
Cell Differentiation
General Medicine
Heparan sulfate
Pathophysiology
immunology and treatment of renal disease
Stoornissen in de biochemische en functionele ontwikkeling van de nier op kinderleeftijd
Middle Aged
Immunohistochemistry
Glomerular Mesangium
medicine.anatomical_structure
Nephrology
Proteoglycans
Heparan sulfate proteoglycans
medicine.medical_specialty
animal structures
Renal function
Enzyme-Linked Immunosorbent Assay
Inborn errors of metabolism
Nephropathy
Disturbances in biochemical and functional development of the kidney during childhood
Fetus
SDG 3 - Good Health and Well-being
Diabetes mellitus
Internal medicine
Genetics
medicine
Humans
Erfelijke stofwisselingsziekten
Aged
Basement membrane
medicine.disease
Culture Media
carbohydrates (lipids)
Endocrinology
Glucose
chemistry
Proteoglycan
nervous system
biology.protein
Heparitin Sulfate
Zdroj: Yard, B A, Kahlert, S, Engelleiter, R, Resch, S, Waldherr, R, Groffen, A J, Van Den Heuvel, L P W J, Van Der Born, J, Berden, J H M, Kröger, S, Hafner, M & Van Der Woude, F J 2001, ' Decreased glomerular expression of agrin in diabetic nephropathy and podocytes, cultured in high glucose medium ', Experimental Nephrology, vol. 9, no. 3, pp. 214-222 . https://doi.org/10.1159/000052614
Scopus-Elsevier
Yard, B A, Kahlert, S, Engelleiter, R, Resch, S, Waldherr, R, Groffen, A J, Van Den Heuvel, L P W J, van den Born, J, Berden, J H M, Kröger, S, Hafner, M & Van Der Woude, F J 2001, ' Decreased glomerular expression of agrin in diabetic nephropathy and podocytes, cultured in high glucose medium ', Experimental Nephrology, vol. 9, no. 3, pp. 214-222 .
Experimental Nephrology, 9, 3, pp. 214-22
Experimental Nephrology, 9, 214-22
Experimental Nephrology, 9(3), 214-222. S. Karger AG
ISSN: 1018-7782
DOI: 10.1159/000052614
Popis: Aim: A decrease in glomerular heparan sulfate (HS) proteoglycan (PG), without apparent decrease in HSPG core protein expression, has been reported to occur in diabetic nephropathy (DN). In most studies however, agrin, the major HSPG core protein in the glomerular basement membrane, has not been studied. This prompted us to study the glomerular expression of agrin in parallel to the expression of HS-glycosaminoglycans (GAG) in biopsies of patients with DN. Furthermore, the influence of glucose on agrin production in cultured podocytes and the expression of agrin in fetal kidneys was investigated. Methods: Cryostat sections of renal biopsies from patients with DN (n = 8) and healthy controls (HC, n = 8), were stained for agrin and HS-GAG. Sections of fetal kidneys were double stained for agrin and CD35 or CD31. Stainings were performed by indirect immunofluorescence (IIF). The production of agrin by cultured human podocytes was tested by ELISA and IIF. Results: The expression of agrin, detected by AS46, was significantly reduced in biopsies from patients with DN compared to HC (p < 0.01). Similar findings were observed when monoclonal antibody JM72 was used (p < 0.05). In addition, a significant reduction in the glomerular expression of HS-GAG was detected with JM403 in these patients (p < 0.01). Agrin is expressed in cultured podocytes, the expression hereof was reduced when the cells were cultured in the presence of 25 mM D-glucose (p < 0.01). In biopsies of human fetal kidneys, glomerular expression of agrin coincided with the expression of CD31. In early stages of glomerular differentiation there was a strong staining for agrin and CD31 while CD35 was only slightly positive. Conclusions: Our data argue against a selective dysregulation in HSPG sulfation in DN, but suggest a pivotal role for hyperglycemia in the downregulation of agrin core protein production.
Databáze: OpenAIRE
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