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

Artikel i vetenskaplig tidskrift
Författare Peidi Liu
Emelie Lassén
V. Nair
C. C. Berthier
M. Suguro
Carina Sihlbom
M. Kretzler
C. Betsholtz
Börje Haraldsson
W. J. Ju
Kerstin Ebefors
Jenny Nyström
Publicerad i Journal of the American Society of Nephrology
Volym 28
Nummer/häfte 10
Sidor 2961-2972
ISSN 1046-6673
Publiceringsår 2017
Publicerad vid Institutionen för neurovetenskap och fysiologi, sektionen för fysiologi
Core Facilities, Proteomics
Sidor 2961-2972
Språk en
Länkar doi.org/10.1681/ASN.2016101103
Ämnesord nitric-oxide-synthase, oxford classification, proliferation, pathogenesis, expression, receptor, disease, level, Urology & Nephrology
Ämneskategorier Urologi och njurmedicin

Sammanfattning

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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