title: Alteration of N-glycosylation in the kidney in a mouse model of systemic lupus erythematosus: relative quantification of N-glycans using an isotope-tagging method.
abstract: Changes in the glycan structures of some glycoproteins have been observed in autoimmune diseases such as systemic lupus erythematosus (SLE) and rheumatoid arthritis. A deficiency of alpha-mannosidase II, which is associated with branching in N-glycans, has been found to induce SLE-like glomerular nephritis in a mouse model. These findings suggest that the alteration of the glycosylation has some link with the development of SLE. An analysis of glycan alteration in the disordered tissues in SLE may lead to the development of improved diagnostic methods and may help to clarify the carbohydrate-related pathogenic mechanism of inflammation in SLE. In this study, a comprehensive and differential analysis of N-glycans in kidneys from SLE-model mice and control mice was performed by using the quantitative glycan profiling method that we have developed previously. In this method, a mixture of deuterium-labelled N-glycans from the kidneys of SLE-model mice and non-labelled N-glycans from kidneys of control mice was analysed by liquid chromatography/mass spectrometry. It was revealed that the low-molecular-mass glycans with simple structures, including agalactobiantennary and paucimannose-type oligosaccharides, markedly increased in the SLE-model mouse. On the other hand, fucosylated and galactosylated complex type glycans with high branching were decreased in the SLE-model mouse. These results suggest that the changes occurring in the N-glycan synthesis pathway may cause the aberrant glycosylations on not only specific glycoproteins but also on most of the glycoproteins in the SLE-model mouse. The changes in glycosylation might be involved in autoimmune pathogenesis in the model mouse kidney.
authors: National Institute of Health Sciences, Setagaya-ku, Tokyo, Japan.
authors: Noritaka
authors: N
authors: Hashii
authors: Nana
authors: N
authors: Kawasaki
authors: Satsuki
authors: S
authors: Itoh
authors: Yukari
authors: Y
authors: Nakajima
authors: Toru
authors: T
authors: Kawanishi
authors: Teruhide
authors: T
authors: Yamaguchi
mesh_terms: D000818:Animals; D002853:Chromatography, Liquid / Q000379:methods; D004195:Disease Models, Animal; D006031:Glycosylation; D007668:Kidney / Q000378:metabolism*; D008180:Lupus Erythematosus, Systemic / Q000378:metabolism*; D008181:Lupus Nephritis / Q000378:metabolism; D013058:Mass Spectrometry / Q000379:methods; D051379:Mice; D019463:Mice, Inbred MRL lpr; D009844:Oligosaccharides / Q000378:metabolism; D011134:Polysaccharides / Q000378:metabolism*
chemical_list: D009844:Oligosaccharides; D011134:Polysaccharides