title: Suppression of adiponectin by aberrantly glycosylated IgA1 in glomerular mesangial cells in vitro and in vivo.
abstract: The pathogenesis of IgA nephropathy (IgAN) may be associated with the mesangial deposition of aberrantly glycosylated IgA1. To identify mediators affected by aberrantly glycosylated IgA1 in cultured human mesangial cells (HMCs), we generated enzymatically modified desialylated and degalactosylated (deSial/deGal) IgA1. The state of deglycosylated IgA1 was confirmed by lectin binding to Helix aspersa (HAA) and Sambucus nigra (SNA). In the cytokine array analysis, 52 proteins were upregulated and 34 were downregulated in HMCs after stimulation with deSial/deGal IgA1. Among them, the secretion of adiponectin was suppressed in HMCs after stimulation with deSial/deGal IgA1. HMCs expressed mRNAs for adiponectin and its type 1 receptor, but not the type 2 receptor. Moreover, we revealed a downregulation of adiponectin expression in the glomeruli of renal biopsy specimens from patients with IgAN compared to those with lupus nephritis. We also demonstrated that aberrantly glycosylated IgA1 was deposited in the mesangium of patients with IgAN by dual staining of HAA and IgA. Moreover, the urinary HAA/SNA ratio of lectin binding was significantly higher in IgAN compared to other kidney diseases. Since adiponectin has anti-inflammatory effects, including the inhibition of adhesion molecules and cytokines, these data suggest that the local suppression of this adipokine by aberrantly glycosylated IgA1 could be involved in the regulation of glomerular inflammation and sclerosis in IgAN.
authors.affiliation: Department of Medicine and Clinical Science, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan.
authors.forename: Tatsuyuki
authors.initials: T
authors.lastname: Inoue
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Sugiyama
authors.forename: Masashi
authors.initials: M
authors.lastname: Kitagawa
authors.forename: Keiichi
authors.initials: K
authors.lastname: Takiue
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Morinaga
authors.forename: Ayu
authors.initials: A
authors.lastname: Ogawa
authors.forename: Yoko
authors.initials: Y
authors.lastname: Kikumoto
authors.forename: Shinji
authors.initials: S
authors.lastname: Kitamura
authors.forename: Yohei
authors.initials: Y
authors.lastname: Maeshima
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Makino
mesh_terms: D052242:Adiponectin / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000818:Animals; D015536:Down-Regulation; D005920:Glomerular Mesangium / Q000166:cytology / Q000378:metabolism*; D005922:Glomerulonephritis, IGA / Q000378:metabolism; D006031:Glycosylation; D006372:Helix, Snails; D007070:Immunoglobulin A / Q000378:metabolism*; D066298:In Vitro Techniques; D008970:Molecular Weight; D009439:Neuraminidase / Q000378:metabolism; D027924:Sambucus nigra; D001616:beta-Galactosidase / Q000378:metabolism
chemical_list: D052242:Adiponectin; D007070:Immunoglobulin A; D009439:Neuraminidase; D001616:beta-Galactosidase