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

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...

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Bibliographic Details
Published in:Scientific reports 2016-10, Vol.6 (1), p.35671-35671, Article 35671
Main Authors: Jiang, Lulu, Hindmarch, Charles C. T., Rogers, Mark, Campbell, Colin, Waterfall, Christy, Coghill, Jane, Mathieson, Peter W., Welsh, Gavin I.
Format: Article
Language:English
Subjects:
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Cell lines
Cells, Cultured
Cytokines
Cytoskeleton
Dexamethasone
Dexamethasone - pharmacology
Down-Regulation - drug effects
Down-Regulation - genetics
Epithelial cells
Epithelial Cells - drug effects
Epithelial Cells - metabolism
Gene Regulatory Networks - drug effects
Gene Regulatory Networks - genetics
Genes
Glucocorticoids
Glucocorticoids - genetics
Growth factors
Humanities and Social Sciences
Humans
Immunomodulation
Immunosuppressive agents
Inflammation
multidisciplinary
Nephropathy
Podocytes - drug effects
Podocytes - metabolism
Ribonucleic acid
RNA
RNA - genetics
Science
Sequence Analysis, RNA - methods
Signal Transduction - drug effects
Signal Transduction - genetics
Steroid hormones
Up-Regulation - drug effects
Up-Regulation - genetics
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Summary: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.
ISSN:2045-2322
2045-2322
DOI:10.1038/srep35671