title: Heparan sulfate of perlecan is involved in glomerular filtration.
abstract: Perlecan is a heparan sulfate proteoglycan and a major component of the glomerular basement membrane. To understand the role of heparan sulfate chains of perlecan in glomerular filtration, detailed analyses were performed of the kidneys of Hspg2(Delta)(3/)(Delta)(3) mice, whose perlecan lacks heparan sulfate attachment sites in N-terminal domain I. Macroscopic, histologic, and electron microscopic observations, as well as immunohistochemical and immunoelectron microscopic analyses using specific antibodies against perlecan and agrin core proteins, revealed no significant abnormalities in these mice under physiologic conditions. Polyethyleneimine staining demonstrated no significant changes in charge density in the glomerular basement membrane. Transcripts of other heparan sulfate proteoglycans, agrin, and collagen type XVIII, as well as perlecan, were expressed at similar levels to those in the wild-type littermates. Approximately 40% of the perlecan synthesized by Hspg2(Delta)(3/)(Delta)(3) fibroblasts was substituted with heparin sulfate and 60% was substituted with chondroitin sulfate. All of the perlecan synthesized by wild-type fibroblasts contained heparin sulfate, indicating an altered substitution of glycosaminoglycans on Hspg2(Delta)(3/)(Delta)(3) perlecan. Immunostaining indicated that the level of chondroitin sulfate was actually increased in the Hspg2(Delta)(3/)(Delta)(3) glomerular basement membrane. When administered intraperitoneally with BSA, Hspg2(Delta)(3/)(Delta)(3) mice exhibited remarkable proteinuria. These findings suggest that heparan sulfate chains of perlecan play an important role in glomerular filtration, especially of a large amount of protein.
authors.affiliation: Division of Nephrology, Department of Medicine, Showa University, Fujigaoka Hospital, Medicine, 1-30 Fujigaoka, Aoba-ku, Yokohama, Kanagawa, 227-8501, Japan. morita@showa-university-fujigaoka.gr.jp
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Morita
authors.forename: Ashio
authors.initials: A
authors.lastname: Yoshimura
authors.forename: Kiyoko
authors.initials: K
authors.lastname: Inui
authors.forename: Terukuni
authors.initials: T
authors.lastname: Ideura
authors.forename: Hideto
authors.initials: H
authors.lastname: Watanabe
authors.forename: Ling
authors.initials: L
authors.lastname: Wang
authors.forename: Raija
authors.initials: R
authors.lastname: Soininen
authors.forename: Karl
authors.initials: K
authors.lastname: Tryggvason
mesh_terms: D000818:Animals; D001485:Basement Membrane / Q000502:physiology; D005919:Glomerular Filtration Rate / Q000502:physiology*; D019812:Heparan Sulfate Proteoglycans / Q000502:physiology*; D007678:Kidney Glomerulus / Q000502:physiology*; D051379:Mice; D023421:Models, Animal
chemical_list: D019812:Heparan Sulfate Proteoglycans; C071927:perlecan