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  • Liu, Peidi,1986Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för fysiologi,Institute of Neuroscience and Physiology, Department of Physiology (author)

Transcriptomic and Proteomic Profiling Provides Insight into Mesangial Cell Function in IgA Nephropathy

  • Article/chapterEnglish2017

Publisher, publication year, extent ...

  • 2017-06-23
  • Ovid Technologies (Wolters Kluwer Health),2017

Numbers

  • LIBRIS-ID:oai:gup.ub.gu.se/258691
  • https://gup.ub.gu.se/publication/258691URI
  • https://doi.org/10.1681/asn.2016101103DOI

Supplementary language notes

  • Language:English

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  • Subject category:ref swepub-contenttype
  • Subject category:art swepub-publicationtype

Notes

  • IgA nephropathy (IgAN), the most common GN worldwide, is characterized by circulating galactose-deficient IgA (gd-IgA) that forms immune complexes. The immune complexes are deposited in the glomerular mesangium, leading to inflammation and loss of renal function, but the complete pathophysiology of the disease is not understood. Using an integrated global transcriptomic and proteomic profiling approach, we investigated the role of the mesangium in the onset and progression of IgAN. Global gene expression was investigated by microarray analysis of the glomerular compartment of renal biopsy specimens from patients with IgAN (n=19) and controls (n=22). Using curated glomerular cell type specific genes from the published literature, we found differential expression of a much higher percentage of mesangial cell positive standard genes than podocyte-positive standard genes in IgAN. Principal coordinate analysis of expression data revealed clear separation of patient and control samples on the basis of mesangial but not podocyte cell positive standard genes. Additionally, patient clinical parameters (serum creatinine values and eGFRs) significantly correlated with Z scores derived from the expression profile of mesangial cell positive standard genes. Among patients grouped according to Oxford MEST score, patients with segmental glomerulosclerosis had a significantly higher mesangial cell positive standard gene Z score than patients without segmental glomerulosclerosis. By investigating mesangial cell proteomics and glomerular transcriptomics, we identified 22 common pathways induced in mesangial cells by gd-IgA, most of which mediate inflammation. The genes, proteins, and corresponding pathways identified provide novel insights into the pathophysiologic mechanisms leading to IgAN.

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  • Lassén, EmelieGothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för fysiologi,Institute of Neuroscience and Physiology, Department of Physiology(Swepub:gu)xlasem (author)
  • Nair, V. (author)
  • Berthier, C. C. (author)
  • Suguro, M. (author)
  • Sihlbom, Carina,1973Gothenburg University,Göteborgs universitet,Core Facilities, Proteomics,Core Facilities, Proteomics(Swepub:gu)xsihca (author)
  • Kretzler, M. (author)
  • Betsholtz, C. (author)
  • Haraldsson, Börje,1957Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för fysiologi,Institute of Neuroscience and Physiology, Department of Physiology(Swepub:gu)xharbo (author)
  • Ju, W. J. (author)
  • Ebefors, Kerstin,1977Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för fysiologi,Institute of Neuroscience and Physiology, Department of Physiology(Swepub:gu)xolker (author)
  • Nyström, Jenny,1972Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för fysiologi,Institute of Neuroscience and Physiology, Department of Physiology(Swepub:gu)xnysje (author)
  • Göteborgs universitetInstitutionen för neurovetenskap och fysiologi, sektionen för fysiologi (creator_code:org_t)

Related titles

  • In:Journal of the American Society of Nephrology: Ovid Technologies (Wolters Kluwer Health)28:10, s. 2961-29721046-66731533-3450

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