{Reference Type}: English Abstract {Title}: [C/EBPβ mediates expressions of downstream inflammatory factors of the tumor necrosis factor-α signaling pathway in renal tubular epithelial cells with NPHP1 knockdown]. {Author}: Huang D;Liu Y;Li D;Zhang J;Yang Y;Sun L; {Journal}: Nan Fang Yi Ke Da Xue Xue Bao {Volume}: 44 {Issue}: 1 {Year}: 2024 Jan 20 暂无{DOI}: 10.12122/j.issn.1673-4254.2024.01.18 {Abstract}: OBJECTIVE: To explore the activation of tumor necrosis factor-α (TNF-α) signaling pathway and the expressions of the associated inflammatory factors in NPHP1-defective renal tubular epithelial cells.
METHODS: A human proximal renal tubular cell (HK2) model of lentivirus-mediated NPHP1 knockdown (NPHP1KD) was constructed, and the expressions of TNF-α, p38, and C/EBPβ and the inflammatory factors CXCL5, CCL20, IL-1β, IL-6 and MCP-1 were detected using RT-qPCR, Western blotting or enzyme-linked immunosorbent assay. A small interfering RNA (siRNA) was transfected in wild-type and NPHP1KDHK2 cells, and the changes in the expressions of TNF-α, p38, and C/EBPβ and the inflammatory factors were examined.
RESULTS: NPHP1KDHK2 cells showed significantly increased mRNA expressions of TNF-α, C/EBPβ, CXCL5, IL-1β, and IL-6 (P < 0.05), protein expressions of phospho-p38 and C/EBPβ (P < 0.05), and IL-6 level in the culture supernatant (P < 0.05), and these changes were significantly blocked by transfection of cells with siRNA-C/EBPβ (P < 0.05).
CONCLUSIONS: TNF-α signaling pathway is activated and its associated inflammatory factors are upregulated in NPHP1KDHK2 cells, and C/EBPβ may serve as a key transcription factor to mediate these changes.