RNA sequencing analysis of human podocytes reveals glucocorticoid regulated gene networks targeting non-immune pathways

Lulu Jiang, Charles C T Hindmarch, Mark Rogers, Colin Campbell, Christy Waterfall, Jane Coghill, Peter W. Mathieson, Gavin I. Welsh*

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)peer-review

15 Citations (Scopus)
268 Downloads (Pure)

Abstract

Glucocorticoids are steroids that reduce inflammation and are used as immunosuppressive drugs for many diseases. They are also the mainstay for the treatment of minimal change nephropathy (MCN), which is characterised by an absence of inflammation. Their mechanisms of action remain elusive. Evidence suggests that immunomodulatory drugs can directly act on glomerular epithelial cells or ‘podocytes’, the cell type which is the main target of injury in MCN. To understand the nature of glucocorticoid effects on non-immune cell functions, we generated RNA sequencing data from human podocyte cell lines and identified the genes that are significantly regulated in dexamethasone-treated podocytes compared to vehicle-treated cells. The upregulated genes are of functional relevance to cytoskeleton-related processes, whereas the downregulated genes mostly encode pro-inflammatory cytokines and growth factors. We observed a tendency for dexamethasone-upregulated genes to be downregulated in MCN patients. Integrative analysis revealed gene networks composed of critical signaling pathways that are likely targeted by dexamethasone in podocytes.
Original languageEnglish
Article number35671
Number of pages11
JournalScientific Reports
Volume6
DOIs
Publication statusPublished - 24 Oct 2016

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