Year: 2016
Type: article
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.
Source: Scientific Reports
DOI: 10.1038/srep33520
Language: English
Subfield: Nephrology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,690
Awards: G1109909514, G1732291147, G3544997728, G359913621, Long-term consequences of HIV in the Kidney, Cellular and molecular mechanisms of retinoids in podocytes, G4313467969, G4687801778, G475021081, Role of HIPK2 in kidney fibrosis, G5340801093, G5377467257, 转录因子C/EBPs在肾纤维化过程中的作用及其机制研究, 辅调节因子SRC及NCoR在介导肾小管上皮细胞炎症因子分泌中作用及干预研究, G5915673765, G7398126575, G8168050404, G8323136698, G9000139470, G9000221455
OpenAlex ID: W2522166009