Transcriptomics

Dataset Information

3

The molecular phenotype of endocapillary proliferation in IgA nephropathy and potential modulation by bioactive small molecules


ABSTRACT: Endocapillary proliferation is associated with higher risk of progressive disease in IgAN. To better understand molecular pathways involved in the development of endocapillary proliferation and to identify novel specific therapeutic targets, we evaluated the glomerular transcriptome of microdissected kidney biopsies from 22 patients with IgAN. Endocapillary proliferation was defined according to the Oxford scoring system by 3 nephropathologists. We analyzed mRNA expression using microarrays and identified transcripts differentially expressed in patients with endocapillary proliferation. Next, we employed both transcription factor analysis and in silico drug screening and confirmed that the endocapillary proliferation transcriptome is significantly enriched with pathways modulated by corticosteroid exposure. With this approach we also identified novel therapeutic targets and bioactive small molecules that may be considered for therapeutic trials for treatment of IgAN. RNA from glomerular compartment was extracted and processed for hybridization on Affymetrix microarrays.

ORGANISM(S): Homo sapiens  

SUBMITTER: Celine C Berthier   Jeff Hodgin  Rohan John  Matthias Kretzler  Hermann-Josef Grone  Stefan Porubsky  Heather N Reich  Elisabeth Grone 

PROVIDER: E-GEOD-50469 | ArrayExpress | 2015-05-18

SECONDARY ACCESSION(S): GSE50469PRJNA217531

REPOSITORIES: GEO, ArrayExpress

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Publications


IgA nephropathy (IgAN) is a clinically and pathologically heterogeneous disease. Endocapillary proliferation is associated with higher risk of progressive disease, and clinical studies suggest that corticosteroids mitigate this risk. However, corticosteroids are associated with protean cellular effects and significant toxicity. Furthermore the precise mechanism by which they modulate kidney injury in IgAN is not well delineated. To better understand molecular pathways involved in the development  ...[more]

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