title: Changes in glomerular mesangium in kidneys with congenital nephrotic syndrome of the Finnish type.
abstract: Congenital nephrotic syndrome of the Finnish type (NPHS1, CNF) is an autosomal recessive disease caused by mutations in a major podocyte protein, nephrin. NPHS1 is associated with heavy proteinuria and the development of glomerular scarring. We studied the cellular and molecular changes affecting the glomerular mesangium in NPHS1 kidneys. Marked hyperplasia of mesangial cells (MC) was mainly responsible for the early mesangial expansion in NPHS1 glomeruli. The levels of the proliferation marker, mindbomb homolog 1 and the major MC mitogen, platelet-derived growth factor, and its receptors, however, were quite normal. Only a small number of cells were positive for CD68 (marker for phagocytic cells) and CD34 (marker for mesenchymal precursor cells) in the NPHS1 mesangium. MCs strongly expressed alpha-smooth muscle actin, indicating myofibloblast transformation. The expression levels of the profibrotic mediators osteopontin and transforming growth factor beta were up-regulated in NPHS1 glomeruli by 3.2 and 1.6-fold, respectively, compared to the controls. The synthesis by MCs of the typical fibroblast products collagen I, fibronectin, and tenascin, however, was low, and the extracellular matrix increase was caused by the accumulation of a normal MC product, collagen IV. The results indicate that severe glomerular sclerosis can develop without major qualitative cellular or molecular changes in the mesangium.
authors.affiliation: Children's Hospital and Biomedicum Helsinki, University of Helsinki, Helsinki, Finland. anne.kaukinen@helsinki.fi
authors.forename: Anne
authors.initials: A
authors.lastname: Kaukinen
authors.forename: Arvi-Matti
authors.initials: AM
authors.lastname: Kuusniemi
authors.forename: Heikki
authors.initials: H
authors.lastname: Helin
authors.forename: Hannu
authors.initials: H
authors.lastname: Jalanko
mesh_terms: D000199:Actins / Q000032:analysis; D000293:Adolescent; D015703:Antigens, CD / Q000032:analysis; D018952:Antigens, CD34 / Q000032:analysis; D015214:Antigens, Differentiation, Myelomonocytic / Q000032:analysis; D001706:Biopsy; D016022:Case-Control Studies; D049109:Cell Proliferation; D002648:Child; D002675:Child, Preschool; D018450:Disease Progression; D016326:Extracellular Matrix Proteins / Q000032:analysis; D005838:Genotype; D005920:Glomerular Mesangium / Q000737:chemistry / Q000473:pathology* / Q000601:surgery; D006801:Humans; D006965:Hyperplasia; D007150:Immunohistochemistry; D007223:Infant; D008565:Membrane Proteins / Q000235:genetics; D050527:Mesangial Cells / Q000737:chemistry / Q000473:pathology*; D008875:Middle Aged; D009154:Mutation; D009392:Nephrectomy; D009404:Nephrotic Syndrome / Q000145:classification / Q000151:congenital / Q000378:metabolism / Q000473:pathology* / Q000601:surgery; D053495:Osteopontin / Q000032:analysis; D010641:Phenotype; D010982:Platelet-Derived Growth Factor / Q000032:analysis; D017479:Receptors, Platelet-Derived Growth Factor / Q000032:analysis; D012598:Sclerosis; D044767:Ubiquitin-Protein Ligases / Q000032:analysis; D000097382:CD68 Molecule
chemical_list: D000199:Actins; D015703:Antigens, CD; D018952:Antigens, CD34; D015214:Antigens, Differentiation, Myelomonocytic; D016326:Extracellular Matrix Proteins; D008565:Membrane Proteins; D053495:Osteopontin; D010982:Platelet-Derived Growth Factor; D017479:Receptors, Platelet-Derived Growth Factor; D044767:Ubiquitin-Protein Ligases; C067980:CD68 antigen, human; D000097382:CD68 Molecule; C506895:SPP1 protein, human; C113267:nephrin; C513496:MIB1 ligase, human