title: RNA sequencing analysis of human podocytes reveals glucocorticoid regulated gene networks targeting non-immune pathways.
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.
authors: Bristol Renal, School of Clinical Sciences, University of Bristol, Bristol, UK.
authors: Lulu
authors: L
authors: Jiang
authors: Department of Biomedical and Molecular Sciences, Queen's University, Kingston, ON, Canada.|Department of Physiology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
authors: Charles C T
authors: CC
authors: Hindmarch
authors: Department of Engineering Mathematics, University of Bristol, Bristol, UK.
authors: Mark
authors: M
authors: Rogers
authors: Department of Engineering Mathematics, University of Bristol, Bristol, UK.
authors: Colin
authors: C
authors: Campbell
authors: Bristol Genomics Facility, School of Biological Sciences, University of Bristol, Bristol, UK.
authors: Christy
authors: C
authors: Waterfall
authors: Bristol Genomics Facility, School of Biological Sciences, University of Bristol, Bristol, UK.
authors: Jane
authors: J
authors: Coghill
authors: President's Office, The University of Hong Kong, Hong Kong, China.
authors: Peter W
authors: PW
authors: Mathieson
authors: Bristol Renal, School of Clinical Sciences, University of Bristol, Bristol, UK.
authors: Gavin I
authors: GI
authors: Welsh
mesh_terms: D002478:Cells, Cultured; D003907:Dexamethasone / Q000494:pharmacology; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism; D053263:Gene Regulatory Networks / Q000187:drug effects / Q000235:genetics*; D005938:Glucocorticoids / Q000235:genetics*; D006801:Humans; D050199:Podocytes / Q000187:drug effects / Q000378:metabolism*; D012313:RNA / Q000235:genetics*; D017423:Sequence Analysis, RNA / Q000379:methods; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics*; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics
chemical_list: D005938:Glucocorticoids; D012313:RNA; D003907:Dexamethasone