| First Author | Zhong F | Year | 2016 |
| Journal | Sci Rep | Volume | 6 |
| Pages | 33520 | PubMed ID | 27644413 |
| Mgi Jnum | J:263572 | Mgi Id | MGI:6101649 |
| Doi | 10.1038/srep33520 | Citation | Zhong F, et al. (2016) Role of C/EBP-alpha in Adriamycin-induced podocyte injury. Sci Rep 6:33520 |
| abstractText | 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-alpha (C/EBP-alpha), a transcription factor known to interact with and activate PPAR-gamma and NF-kappaB, is suppressed in the glomerular cells, particularly in podocytes, in human kidneys with focal segmental glomerulosclerosis. Genetic ablation of C/EBP-alpha 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-alpha in human podocytes in vitro led to an inhibition of MCP-1 and IL-6 expression in response to TNF-alpha and IL-1beta treatments. Conversely, augmented production of MCP-1 and IL-6 was observed in the glomeruli of C/EBP-alpha knockout mice and was associated increased infiltration of macrophages in vivo. Together, our data suggest that C/EBP-alpha mediates anti-inflammatory effects in podocytes to confer protection against podocyte injury and loss that may contribute to worsening glomerulosclerosis. |
