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

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.

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Hodgin JB, Berthier CC, John R, Grone E, Porubsky S, Gröne HJ, Herzenberg AM, Scholey JW, Hladunewich M, Cattran DC, Kretzler M, Reich HN