BIOMEDICAL C/EBP 13 Mediates the Aberrant Inflammatory Response and Cell Cycle Arrest in Lps-stimulated Human Renal Tubular Epithelial Cells by Regulating NF- KB Pathway

摘要

Background and Aims. The main cause of sepsis-induced Acute kidney injury (AKI) is acute infection after surgery and subsequent progression. However, the mechanism by which AKI is caused and developed from sepsis are not completely known. Herein, we determined the role of CCAAT/enhancer-binding protein 13 (C/EBP 13) in sepsis-induced AKI Methods. C/EBP 13 expression was up or down-regulated in LPS-stimulated human renal tubular epithelial cells in vitro by recombinant adenoviruses or siRNA. Subsequent analyses included the test of TNF- a and IL-6 levels by ELISA, cell cycle assay by flow cytometry. Results. C/EBP 13 was aberrantly expressed in renal tubular epithelial HK-2 cells exposed to LPS. C/EBP beta overexpression significantly enhanced, but C/EBP 13 silencing obviously decreased the production and secretion of inflammatory cytokines TNF- a and IL-6 induced by LPS stimulus in HK-2 cells. And the cell cycle arrest of HK-2 cells induced by LPS was also enhanced after C/EBP beta overexpression while attenuated after C/EBP 13 silencing. Consistent pattern of changes in Cyclin D1 and p21 expression were observed in LPS-stimulated HK-2 cells after C/EBP 13 silencing and C/EBP 13 overexpression. Additionally, the increased p-NF- KB levels induced by LPS were found to be obviously decreased after C/EBP 13 silencing in HK-2 cells. And the enhanced TNF- a and IL-6 secretion as well as cell cycle arrest by C/EBP beta overexpression were blocked by BAY11-7082 inhibitor of NF- KB pathway. Conclusions. C/EBP 13 could mediate the LPS-induced aberrant inflammatory response and cell cycle arrest in tubular epithelial cells by NF- KB pathway. (c) 2021 Instituto Mexicano del Seguro Social (IMSS). Published by Elsevier Inc. All rights reserved.