title: Role of C/EBP-α in Adriamycin-induced podocyte injury.
abstract: Podocytes are terminally differentiated epithelial cells in the kidney glomeruli that act as a key component of the glomerular filtration barrier. Although the inciting injury to the podocyte may vary between various glomerular diseases, the inevitable consequence of podocyte injury results in their loss, leading to progressive kidney disease. Here, we report that the expression of CCAAT/enhancer binding protein-α (C/EBP-α), a transcription factor known to interact with and activate PPAR-γ and NF-κB, is suppressed in the glomerular cells, particularly in podocytes, in human kidneys with focal segmental glomerulosclerosis. Genetic ablation of C/EBP-α in podocytes resulted in increased proteinuria, increased podocyte foot process effacement, and to decreased podocyte number in the setting of Adriamycin (ADR)-induced nephropathy. Overexpression of C/EBP-α in human podocytes in vitro led to an inhibition of MCP-1 and IL-6 expression in response to TNF-α and IL-1β treatments. Conversely, augmented production of MCP-1 and IL-6 was observed in the glomeruli of C/EBP-α knockout mice and was associated increased infiltration of macrophages in vivo. Together, our data suggest that C/EBP-α mediates anti-inflammatory effects in podocytes to confer protection against podocyte injury and loss that may contribute to worsening glomerulosclerosis.
authors.affiliation: Institute of Nephrology, Shanghai Jiaotong University School of Medicine, Shanghai, China.|Division of Nephrology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors.forename: Fang
authors.initials: F
authors.lastname: Zhong
authors.affiliation: Institute of Nephrology, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Weiming
authors.initials: W
authors.lastname: Wang
authors.affiliation: Division of Nephrology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors.forename: Kyung
authors.initials: K
authors.lastname: Lee
authors.affiliation: Division of Nephrology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors.forename: John Cijiang
authors.initials: JC
authors.lastname: He
authors.affiliation: Institute of Nephrology, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Nan
authors.initials: N
authors.lastname: Chen
mesh_terms: D000818:Animals; D022763:CCAAT-Enhancer-Binding Protein-alpha / Q000378:metabolism*; D016207:Cytokines / Q000096:biosynthesis; D004317:Doxorubicin / Q000009:adverse effects*; D005923:Glomerulosclerosis, Focal Segmental / Q000150:complications / Q000378:metabolism / Q000473:pathology; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D050527:Mesangial Cells / Q000378:metabolism / Q000473:pathology; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D050199:Podocytes / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D011507:Proteinuria / Q000150:complications / Q000378:metabolism / Q000473:pathology
chemical_list: D022763:CCAAT-Enhancer-Binding Protein-alpha; D016207:Cytokines; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C407223:NPHS2 protein; C113267:nephrin; D004317:Doxorubicin